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Repert. med. cir ; 30(1): 13-21, 2021. Ilus., tab.
Article in English | LILACS, COLNAL | ID: biblio-1281415


El gen AIP (proteína moduladora de la actividad del receptor de aril hidrocarburos) se localiza en la región 11q13.2 y codifica para una proteína de 330 aminoácidos que interactúa con el factor de transcripción AhR (receptor para aril hidrocarburos). Las mutaciones en este gen se han asociado con adenomas pituitarios aislados de tipo familiar (APAF). Se caracterizan por una presentación temprana (alrededor de 20 años), por lo regular producen hormona de crecimiento y/o prolactina, tienen un comportamiento clínico agresivo y poca respuesta a análogos de somatostatina.

The AIP gene (aryl hydrocarbon receptor interacting protein) is located on chromosome 11q13.2 and encodes a 330 amino acid protein which interacts with the aryl hydrocarbon receptor (AHR) transcription factor. Mutations in the AIP gene have been associated with familial isolated pituitary adenomas (FIPA). They characterize by an early-onset (around the age of 20 years old) and for being aggressive, growth hormone and/or prolactin-secreting tumors, with poor response to somatostatin analogues.

Humans , Animals , Male , Female , Child , Adolescent , Adult , Young Adult , Pituitary Neoplasms/genetics , Pituitary Neoplasms/metabolism , Adenoma/genetics , Adenoma/metabolism , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Pituitary Diseases/genetics , Pituitary Diseases/metabolism
Rev. bras. oftalmol ; 79(1): 71-80, Jan.-Feb. 2020. tab, graf
Article in Portuguese | LILACS | ID: biblio-1092653


Resumo Atualmente a membra amniótica (MA) tem obtido importância devido à comprovada capacidade de reduzir inflamação, auxiliar a cicatrização e epitelização, possuindo propriedades antimicrobianas e antivirais, além de baixa imunogenicidade. As indicações de seu uso na oftalmologia têm aumentado muito nas duas últimas décadas. Objetivo: Descrever a estrutura básica e as propriedades biológicas da MA em relação aos componentes da sua matriz extracelular e fatores de crescimento, as consequências de diferentes técnicas empregadas na sua preservação e esterilização, métodos para remoção do epitélio e a comparação dos custos dos diferentes meios de conservação atualmente empregados. Métodos: Pesquisa nas bases de dados do Portal da Biblioteca Virtual em Saúde (BVS), Pubmed, Cochrane, Scielo e Lilacs com as palavras-chave: membrana amniótica, transplante, reconstrução da córnea, doenças da conjuntiva. Resultados: A literatura é vasta na descrição dos efeitos de diversos agentes e técnicas na preparação da MA, dentre elas sua preservação, esterilização e desepitelização. A membrana desnuda tem sido a escolha para a reconstrução da superfície ocular, pois facilita a cicatrização. Em relação aos agentes conservantes, o glicerol é o meio mais utilizado mundialmente pelo baixo custo e facilidade de manuseio. Conclusão: A comparação das diversas técnicas nos guia na elaboração de protocolos de preparo da MA para uso oftalmológico. A membrana desnuda facilita a cicatrização em relação a com células epiteliais. O glicerol é o meio de conservação mais utilizado pelo baixo custo e facilidade de manuseio.

Abstract Currently, the amniotic membrane (AM) has obtained importance due to its ability to reduce inflammation, helping in the healing and epithelialization processes, having antimicrobial and antiviral properties and low immunogenicity. Its indications in ophthalmology have increased considerably in the past two decades. Objective: To describe the basic structure and biological properties of the AM, the components of the extracellular matrix and growth factors, the consequences of different techniques used in its preservation, and sterilization methods for the epithelium removal. To compare the costs of the different preservation solutions currently employed. Study design: literature review. Methods: Research in BVS databases, PubMed, Cochrane, Scielo and Lilacs with keywords: amniotic membrane transplantation, corneal reconstruction, conjunctival diseases. Results: The literature is vast in describing the effects of different agents and techniques used in the preparation of MA, including its preservation, sterilization and desepithelization. The naked membrane is the choice to reconstruct the ocular surface, as it facilitates the healing course. Regarding the preservatives, glycerol is the most used worldwide due its low cost and easy handling. Conclusion: Comparing different techniques guides us in developing a MA preparation protocol for ophthalmic use. The naked membrane facilitates the healing process compared with the presence of epithelial cells. The glycerol is the most used preservation method because of its low cost and easy handling.

Humans , Tissue Preservation/methods , Conjunctival Diseases/surgery , Corneal Diseases/surgery , Tissue and Organ Harvesting/methods , Eye Diseases/surgery , Amnion/transplantation , Tissue Banks/standards , Tissue Donors/supply & distribution , Wound Healing , Biological Dressings/standards , Biological Products/standards , Tissue and Organ Procurement/standards , Cryopreservation/methods , Sterilization/methods , Collagen/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Extracellular Matrix/metabolism , Amnion/cytology , Amnion/microbiology , Amnion/ultrastructure
Arch. endocrinol. metab. (Online) ; 63(4): 438-444, July-Aug. 2019. tab, graf
Article in English | LILACS | ID: biblio-1019366


ABSTRACT Pubertal timing in humans is determined by complex interactions including hormonal, metabolic, environmental, ethnic, and genetic factors. Central precocious puberty (CPP) is defined as the premature reactivation of the hypothalamic-pituitary-gonadal axis, starting before the ages of 8 and 9 years in girls and boys, respectively; familial CPP is defined by the occurrence of CPP in two or more family members. Pioneering studies have evidenced the participation of genetic factors in pubertal timing, mainly identifying genetic causes of CPP in sporadic and familial cases. In this context, rare activating mutations were identified in genes of the kisspeptin excitatory pathway (KISS1R and KISS1 mutations). More recently, loss-of-function mutations in two imprinted genes (MKRN3 and DLK1) have been identified as important causes of familial CPP, describing novel players in the modulation of the hypothalamic-pituitary-gonadal axis in physiological and pathological conditions. MKRN3 mutations are the most common cause of familial CPP, and patients with MKRN3 mutations present clinical features indistinguishable from idiopathic CPP. Meanwhile, adult patients with DLK1 mutations present high frequency of metabolic alterations (overweight/obesity, early onset type 2 diabetes and hyperlipidemia), indicating that DLK1 may be a novel link between reproduction and metabolism. Arch Endocrinol Metab. 2019;63(4):438-44

Humans , Puberty, Precocious/genetics , Phenotype , Puberty, Precocious/etiology , Ribonucleoproteins/genetics , Calcium-Binding Proteins , Gene Silencing , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Kisspeptins/genetics , Receptors, Kisspeptin-1/genetics , Membrane Proteins/genetics , Membrane Proteins/metabolism , Methylation , Mutation
Biol. Res ; 51: 10, 2018. tab, graf
Article in English | LILACS | ID: biblio-950896


PROPOSE: We aimed to explore the potential molecular mechanism and independent prognostic genes for colon cancer (CC). METHODS: Microarray datasets GSE17536 and GSE39582 were downloaded from Gene Expression Omnibus. Meanwhile, the whole CC-related dataset were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNA (DEMs) were identified between cancer tissue samples and para-carcinoma tissue samples in TCGA dataset, followed by the KEGG pathway and GO function analyses. Furthermore, the clinical prognostic analysis including overall survival (OS) and disease-free survival (DFS) were performed in all three datasets. RESULTS: A total of 633 up- and 321 down-regulated mRNAs were revealed in TCGA dataset. The up-regulated mRNAs were mainly assembled in functions including extracellular matrix and pathways including Wnt signaling. The down-regulated mRNAs were mainly assembled in functions like Digestion and pathways like Drug metabolism. Furthermore, up-regulation of UL16-binding protein 2 (ULBP2) was associated with OS in CC patients. A total of 12 DEMs including Surfactant Associated 2 (SFTA2) were potential DFS prognostic genes in CC patients. Meanwhile, the GRP and Transmembrane Protein 37 (TMEM37) were two outstanding independent DFS prognostic genes in CC. CONCLUSIONS: ULBP2 might be a potential novel OS prognostic biomarker in CC, while GRP and TMEM37 could be served as the independent DFS prognostic genes in CC. Furthermore, functions including extracellular matrix and digestion, as well as pathways including Wnt signaling and drug metabolism might play important roles in the process of CC.

Humans , Animals , Colonic Neoplasms/diagnosis , Colonic Neoplasms/genetics , Gene Expression Profiling/methods , RNA, Messenger/genetics , RNA, Messenger/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Genetic Markers , Down-Regulation/genetics , Gene Expression Regulation, Neoplastic , Up-Regulation/genetics , Risk Factors , Colonic Neoplasms/metabolism , Disease-Free Survival , Gastrin-Releasing Peptide/genetics , Gastrin-Releasing Peptide/metabolism , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Pulmonary Surfactant-Associated Protein A/genetics , Pulmonary Surfactant-Associated Protein A/metabolism , Microarray Analysis , Murinae , Kaplan-Meier Estimate , GPI-Linked Proteins/genetics , GPI-Linked Proteins/metabolism
Biol. Res ; 51: 31, 2018. graf
Article in English | LILACS | ID: biblio-983936


BACKGROUND: miR-214 was demonstrated to be upregulated in models of renal disease and promoted fibrosis in renal injury independent of TGF-ß signaling in vivo. However, the detailed role of miR-214 in acute kidney injury (AKI) and its underlying mechanism are still largely unknown. METHODS: In this study, an I/R-induced rat AKI model and a hypoxia-induced NRK-52E cell model were used to study AKI. The concentrations of kidney injury markers serum creatinine, blood urea nitrogen, and kidney injury molecule-1 were measured. The expressions of miR-214, tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, were detected by RT-qPCR. The protein levels of Bcl-2, Bax, Dickkopf-related protein 3, ß-catenin, c-myc, and cyclinD1 were determined by western blot. Cell apoptosis and caspase 3 activity were evaluated by flow cytometry analysis and caspase 3 activity assay, respectively. Luciferase reporter assay was used to confirm the interaction between miR-214 and Dkk3. RESULTS: miR-214 expression was induced in ischemia-reperfusion (I/R)-induced AKI rat and hypoxic incubation of NRK-52E cells. Overexpression of miR-214 alleviated hypoxia-induced NRK-52E cell apoptosis while inhibition of miR-214 expression exerted the opposite effect. Dkk3 was identified as a target of miR-214. Anti-miR-214 abolished the inhibitory effects of DKK3 knockdown on hypoxia-induced NRK-52E cell apoptosis by inactivation of Wnt/ß-catenin signaling. Moreover, miR-214 ameliorated AKI in vivo by inhibiting apoptosis and fibrosis through targeting Dkk3 and activating Wnt/ß -catenin pathway. CONCLUSION: miR-214 ameliorates AKI by inhibiting apoptosis through targeting Dkk3 and activating Wnt/ß -catenin signaling pathway, offering the possibility of miR-214 in the therapy of ischemic AKI.

Animals , Male , Rats , Intercellular Signaling Peptides and Proteins/metabolism , MicroRNAs/metabolism , Catenins/metabolism , Acute Kidney Injury/metabolism , Wnt Signaling Pathway/genetics , Rats, Sprague-Dawley , Chemokines , Intercellular Signaling Peptides and Proteins/genetics , MicroRNAs/genetics , Adaptor Proteins, Signal Transducing , Cell Proliferation , Disease Models, Animal , Catenins/genetics , Acute Kidney Injury/chemically induced
J. pediatr. (Rio J.) ; 91(2): 196-205, Mar-Apr/2015. tab
Article in English | LILACS | ID: lil-745942


OBJECTIVE: This study aimed to evaluate the association of junk food consumption with hypertension and obesity in a national sample of Iranian children and adolescents. METHODS: This nationwide study was conducted in 2011-2012 among 14,880 students, aged 6-18 years, selected by cluster sampling from 30 provinces. Weight, height, waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), as well as systolic and diastolic blood pressure (BP) were measured. Junk food was divided into four categories, including salty snacks, sweets, sweetened beverages, and fast food. Subjects reported how many times they had consumed each item (daily, weekly, and seldom). RESULTS: The intake of sweets was significantly associated with anthropometric indices and BP levels. Moreover, a significant association was found between fast food consumption, BP levels, and anthropometric indices (except for WHtR and WHR). Sweet beverages consumption was significantly associated with anthropometric indices; however, the consumption of salty snacks was only significantly associated with height, HC, and WHR. The risk of general obesity (OR: 0.75, 95% CI: 0.65-0.87) and abdominal obesity (OR: 0.81, 95% CI: 0.72-0.92) among participants who seldom consumed sweets was less than those who consumed daily. Also, the risk of general obesity (OR: 0.85, 95% CI: 0.74-0.97) among students that seldom consumed sweetened beverages was less than subjects who consumed them on a daily basis. CONCLUSION: It was found that junk food consumption increased the risk of both general and abdominal obesity; therefore, consumption of junk food should be reduced via restricting TV advertisements and increasing taxes on junk foods. .

OBJETIVO: Avaliar a associação entre o consumo de junk food e a hipertensão e obesidade em uma amostra nacional de crianças e adolescentes iranianos. MÉTODOS: Este estudo nacional foi feito entre 2011 e 2012 com 14.880 estudantes com seis-18 anos, selecionados por amostra em bloco em 30 províncias. Foram medidos o peso, a estatura, a circunferência da cintura (CC), a circunferência do quadril (CQ), a razão cintura/quadril (RCQ), a razão cintura/estatura (RCE) e a pressão arterial sistólica e diastólica (PAS e PAD). A junk food foi dividida em quatro categorias, incluindo lanches salgados, doces, bebidas açucaradas e fast food. Os indivíduos relataram quantas vezes consumiam cada um dos itens (diariamente, semanalmente, raramente). RESULTADOS: O consumo de doces foi associado significativamente aos índices antropométricos e níveis de pressão arterial (PA). Além disso, havia uma associação significativa entre o consumo de fast food e os níveis de PA e os índices antropométricos (exceto RCE e RCQ). O consumo de bebidas açucaradas foi associado significativamente aos índices antropométricos, porém o consumo de lanches salgados foi associado significativamente apenas a estatura, CQ e RCQ. O risco de obesidade geral (RC: 0,75, IC de 95%: 0,65-0,87) e obesidade abdominal (RC: 0,81, IC de 95%: 0,72-0,92) entre participantes que raramente consumiam doces era menor do que naqueles que os consumiam diariamente. Além disso, o risco de obesidade geral (RC: 0,85; IC de 95%: 0,74-0,97) entre estudantes que raramente consumiam bebidas açucaradas era menor do que entre indivíduos que os consumiam diariamente. CONCLUSÃO: Constatamos que o consumo de junk food aumentou o risco de obesidade geral e abdominal; portanto, o consumo de junk food deve ser reduzido por meio da restrição de comerciais de TV e do aumento de impostos sobre esse tipo de alimento. .

Female , Humans , Autophagy , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Intercellular Signaling Peptides and Proteins/metabolism , Signal Transduction , Stress, Physiological , Biomarkers, Tumor/metabolism , Amino Acid Sequence , Breast Neoplasms/enzymology , Environment , Extracellular Signal-Regulated MAP Kinases/metabolism , /metabolism , Molecular Sequence Data , Phosphorylation , Protein Biosynthesis , /metabolism , Phosphopeptides/chemistry , Phosphopeptides/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Temperature
Dental press j. orthod. (Impr.) ; 20(1): 45-51, Jan-Feb/2015. tab, graf
Article in English | LILACS | ID: lil-741446


INTRODUCTION: The consensus about the relationship between TMD and orthodontic treatment has gone from a cause and effect association between TMD and orthodontic treatment to the idea that there is no reliable evidence supporting this statement. OBJECTIVE: To assess the beliefs, despite scientific evidence, of Brazilian orthodontists about the relationship between TMD and orthodontic treatment with regards to treatment, prevention and etiology of TMD. METHODS: A survey about the relationship between TMD and orthodontic treatment was prepared and sent to Brazilian orthodontists by e-mail and social networks. Answers were treated by means of descriptive statistics and strong associations between variables were assessed by qui-square test. RESULTS: The majority of orthodontists believe that orthodontic treatment not only is not the best treatment option for TMD, but also is not able to prevent TMD. Nevertheless, the majority of orthodontists believe that orthodontic treatment can cause TMD symptoms. CONCLUSION: This study suggests that orthodontists' beliefs about the relationship between orthodontic treatment and TMD are in accordance with scientific evidence only when referring to treatment and prevention of TMD. The majority of orthodontists believe that, despite scientific evidence, orthodontic treatment can cause TMD. .

INTRODUÇÃO: o consenso sobre a relação entre DTM e tratamento ortodôntico foi de uma associação de causa e efeito à ideia de que não há evidências confiáveis que suportem essa afirmação. OBJETIVO: avaliar as crenças, sem considerar as evidências, de ortodontistas brasileiros sobre a relação entre DTM e tratamento ortodôntico com relação ao tratamento, prevenção e etiologia da DTM. MÉTODOS: um questionário sobre a relação entre DTM e tratamento ortodôntico foi preparado e enviado a ortodontistas brasileiros por meio de e-mail e mídias sociais. As respostas foram analisadas por estatística descritiva, e fortes associações entre as variáveis foram verificadas pelo teste χ2. RESULTADOS: a maioria dos ortodontistas acredita que o tratamento ortodôntico não é o melhor tratamento para DTM. Além disso, acreditam que não é a melhor forma para sua prevenção. Também, a maioria dos ortodontistas acredita que o tratamento ortodôntico pode causar sintomas de DTM. CONCLUSÃO: este estudo sugere que as crenças dos ortodontistas sobre a relação entre tratamento ortodôntico e DTM estão de acordo com as evidências científicas apenas quando se trata do tratamento e da prevenção de DTM. A maioria dos ortodontistas acredita que, apesar das evidências científicas, o tratamento ortodôntico pode causar DTM. .

Humans , Cell Cycle Proteins/metabolism , DNA Replication/genetics , Forkhead Transcription Factors/metabolism , G1 Phase/physiology , Gene Expression Regulation/genetics , Protein-Serine-Threonine Kinases/metabolism , Replication Origin/genetics , Signal Transduction/genetics , Blotting, Western , Cell Fractionation , Cell Line , Cell Cycle Proteins/genetics , /metabolism , DNA Primers/genetics , Fluorescent Antibody Technique , Forkhead Transcription Factors/genetics , Immunoblotting , Immunoprecipitation , Intercellular Signaling Peptides and Proteins/metabolism , Protein-Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins c-myc/metabolism , Reverse Transcriptase Polymerase Chain Reaction , RNA Interference
Braz. j. med. biol. res ; 47(4): 299-306, 8/4/2014. graf
Article in English | LILACS | ID: lil-705762


Notch signaling plays a vital role in tumorigenicity and tumor progression by regulating proliferation, invasion, and the tumor microenvironment. Previous research by our group indicated that Notch ligand Delta-like 1 (Dll1) is involved in angiogenesis in melanoma, and we noticed that it took a longer time to trypsinize Dll1-expressing B16 melanoma cells than the control cells. In this article, we extended our study to investigate the effects of Dll1 on tumor cell adhesion and metastasis. Dll1 overexpression activated Notch signaling in B16 tumor cells and significantly enhanced the adhering capacity of B16 tumor cells both in vitro and in vivo. B16-Dll1 cells also had a higher metastatic potential than their counterpart in the mouse model of lung metastasis. Along with increased Dll1 expression, N-cadherin, but not E-cadherin, was upregulated in B16-Dll1 cells. These data suggested that Notch ligand Dll1 may enhance the adhesion and metastasis of melanoma cells by upregulation of N-cadherin.

Animals , Cadherins/biosynthesis , Intercellular Signaling Peptides and Proteins/metabolism , Lung Neoplasms/secondary , Melanoma, Experimental/secondary , Membrane Proteins/metabolism , Signal Transduction/genetics , Blotting, Western , Cell Adhesion , Cell Culture Techniques , Cell Line, Tumor , Gene Expression , Green Fluorescent Proteins , Human Umbilical Vein Endothelial Cells/physiology , Melanoma, Experimental/pathology , Real-Time Polymerase Chain Reaction , Up-Regulation
Article in English | WPRIM | ID: wpr-163317


The purpose of this study was to elucidate the origin and cellular composition of retrocorneal membranes (RCMs) associated with chemical burns using immunohistochemical staining for primitive cell markers. Six cases of RCMs were collected during penetrating keratoplasty. We examined RCMs with hematoxylin and eosin (H&E), periodic acid-Schiff (PAS) staining and immunohistochemical analysis using monoclonal antibodies against hematopoietic stem cells (CD34, CD133, c-kit), mesenchymal stem cells (beta-1-integrin, TGF-beta, vimentin, hSTRO-1), fibroblasts (FGF-beta, alpha-smooth muscle actin), and corneal endothelial cells (type IV collagen, CD133, VEGF, VEGFR1). Histologic analysis of RCMs revealed an organized assembly of spindle-shaped cells, pigment-laden cells, and thin collagenous matrix structures. RCMs were positive for markers of mesenchymal stem cells including beta-1-integrin, TGF-beta, vimentin, and hSTRO-1. Fibroblast markers were also positive, including FGF-beta and alpha-smooth muscle actin (SMA). In contrast, immunohistochemical staining was negative for hematopoietic stem cell markers including CD34, CD133 and c-kit as well as corneal endothelial cell markers such as type IV collagen, CD133 except VEGF and VEGFR1. Pigment-laden cells did not stain with any antibodies. The results of this study suggest that RCMs consist of a thin collagen matrix and fibroblast-like cells and may be a possible neogenetic structure produced from a lineage of bone marrow-derived mesenchymal stem cells.

Adult , Aged , Antigens, CD/metabolism , Cornea/cytology , Cytokines/metabolism , Endothelial Cells/cytology , Female , Fibroblasts/cytology , Hematopoietic Stem Cells/cytology , Humans , Immunohistochemistry , Intercellular Signaling Peptides and Proteins/metabolism , Male , Mesenchymal Stem Cells/cytology , Middle Aged , Stem Cells/cytology
Article in English | WPRIM | ID: wpr-122147


Platelet-rich plasma (PRP) contains growth factors that promote tissue regeneration. Previously, we showed that heparin-conjugated fibrin (HCF) exerts the sustained release of growth factors with affinity for heparin. Here, we hypothesize that treatment of skin wound with a mixture of PRP and HCF exerts sustained release of several growth factors contained in PRP and promotes skin wound healing. The release of fibroblast growth factor 2, platelet-derived growth factor-BB, and vascular endothelial growth factor contained in PRP from HCF was sustained for a longer period than those from PRP, calcium-activated PRP (C-PRP), or a mixture of fibrin and PRP (F-PRP). Treatment of full-thickness skin wounds in mice with HCF-PRP resulted in much faster wound closure as well as dermal and epidermal regeneration at day 12 compared to treatment with either C-PRP or F-PRP. Enhanced skin regeneration observed in HCF-PRP group may have been at least partially due to enhanced angiogenesis in the wound beds. Therefore, this method could be useful for skin wound treatment.

Animals , Blotting, Western , Cell Proliferation , Dermis/cytology , Female , Fibrin/metabolism , Fibroblast Growth Factor 2/genetics , Heparin/metabolism , Immunoenzyme Techniques , Intercellular Signaling Peptides and Proteins/metabolism , Mice , Mice, Inbred BALB C , Platelet-Rich Plasma/metabolism , Proto-Oncogene Proteins c-sis/genetics , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Regeneration , Skin/cytology , Vascular Endothelial Growth Factor A/genetics , Wound Healing/physiology
Braz. j. med. biol. res ; 43(1): 17-24, Jan. 2010. tab, ilus
Article in English | LILACS | ID: lil-535634


We have demonstrated that a synthetic DNA enzyme targeting early growth response factor-1 (Egr-1) can inhibit neointimal hyperplasia following vascular injury. However, the detailed mechanism of this inhibition is not known. Thus, the objective of the present study was to further investigate potential inhibitory mechanisms. Catalytic DNA (ED5) and scrambled control DNA enzyme (ED5SCR) were synthesized and transfected into primary cultures of rat vascular smooth muscle cells (VSMCs). VSMC proliferation and DNA synthesis were analyzed by the MTT method and BrdU staining, respectively. Egr-1, TGF-â1, p53, p21, Bax, and cyclin D1 expression was detected by RT-PCR and Western blot. Apoptosis and cell cycle assays were performed by FACS. Green fluorescence could be seen localized in the cytoplasm of 70.6 ± 1.52 and 72 ± 2.73 percent VSMCs 24 h after transfection of FITC-labeled ED5 and ED5SCR, respectively. We found that transfection with ED5 significantly inhibited cultured VSMC proliferation in vitro after 24, 48, and 72 h of serum stimulation, and also effectively decreased the uptake of BrdU by VSMC. ED5 specifically reduced serum-induced Egr-1 expression in VSMCs, further down-regulated the expression of cyclin D1 and TGF-â1, and arrested the cells at G0/G1, inhibiting entry into the S phase. FACS analysis indicated that there was no significant difference in the rate of apoptosis between ED5- and ED5SCR-transfected cells. Thus, ED5 can specifically inhibit Egr-1 expression, and probably inhibits VSMC proliferation by down-regulating the expressions of cyclin D1 and TGF-â1. However, ED5 has no effect on VSMC apoptosis.

Animals , Rats , Cell Proliferation , Cyclin D1/metabolism , Early Growth Response Protein 1/antagonists & inhibitors , Intercellular Signaling Peptides and Proteins/physiology , Muscle, Smooth, Vascular/cytology , Transforming Growth Factor beta1/metabolism , Apoptosis/physiology , Blotting, Western , Catalytic Domain/physiology , Cyclin D1/physiology , DNA , Down-Regulation/physiology , Hyperplasia/prevention & control , Intercellular Signaling Peptides and Proteins/metabolism , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Tunica Intima/pathology
Arq. bras. endocrinol. metab ; 52(4): 599-610, jun. 2008. ilus, tab
Article in Portuguese | LILACS | ID: lil-485826


Os tumores hipofisários, adenomas em sua quase totalidade, são de ocorrência freqüente, representando 10 por cento a 15 por cento de todas as neoplasias intracranianas. Estas lesões são classificadas em microadenomas (< 10 mm) ou macroadenomas (> 10 mm) e como secretoras ou quiescentes (não-funcionantes). Estes tumores são capazes de secretar, de maneira autônoma, os hormônios adenohipofisários, como o hormônio de crescimento (GH), a prolactina (PRL), o hormônio adrenocorticotrófico (ACTH), o hormônio tireotrófico (TSH), o hormônio folículo estimulante (FSH) e o hormônio luteinizante (LH). A ocorrência de metástase, caracterizando um carcinoma hipofisário, é bastante rara, mas são relativamente comuns tumores de comportamento agressivo que exibem sinais de invasão local. Embora a sua patogênese ainda não seja plenamente caracterizada, muitos mecanismos moleculares envolvidos na tumorigênese hipofisária já foram desvendados. Nesta revisão, serão descritos avanços consideráveis realizados na última década relativos à compreensão dos fatores envolvidos na progressão tumoral, incluindo a participação de oncogenes, supressores tumorais e fatores de crescimento.

Pituitary tumors, almost invariably adenomas, are of frequent occurrence, accounting for 10 percent to 15 percent of all the intracranial neoplasm. They are classified as microadenomas (< 10 mm) or macroadenomas (> 10 mm) and as secreting or clinically non-secreting (or not functioning) adenomas. These tumors are autonomously capable to release pituitary hormones such as the growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The occurrence of metastases, characterizing a pituitary carcinoma, is exceedingly rare. However tumors with aggressive behavior, leading to local invasion, are relatively common. Although the pathogenesis of pituitary tumors is fully characterized, many molecular mechanisms of pituitary tumorigenesis had already been revealed. This review intents to describe advances in the understanding of the involved advances that have been made in the last decade concerning pituitary tumors progression, including the participation of oncogenes, tumor suppressor genes and growth factors.

Humans , Genes, Tumor Suppressor/physiology , Intercellular Signaling Peptides and Proteins/genetics , Pituitary Neoplasms/genetics , Cell Cycle/physiology , /genetics , Intercellular Signaling Peptides and Proteins/metabolism , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/pathology
Braz. j. med. biol. res ; 39(11): 1373-1385, Nov. 2006. ilus, graf
Article in English | LILACS | ID: lil-437829


The successful implantation of the blastocyst depends on adequate interactions between the embryo and the uterus. The development of the embryo begins with the fertilized ovum, a single totipotent cell which undergoes mitosis and gives rise to a multicellular structure named blastocyst. At the same time, increasing concentrations of ovarian steroid hormones initiate a complex signaling cascade that stimulates the differentiation of endometrial stromal cells to decidual cells, preparing the uterus to lodge the embryo. Studies in humans and in other mammals have shown that cytokines and growth factors are produced by the pre-implantation embryo and cells of the reproductive tract; however, the interactions between these factors that converge for successful implantation are not well understood. This review focuses on the actions of interleukin-1, leukemia inhibitory factor, epidermal growth factor, heparin-binding epidermal growth factor, and vascular endothelial growth factor, and on the network of their interactions leading to early embryo development, peri-implantatory endometrial changes, embryo implantation and trophoblast differentiation. We also propose therapeutical approaches based on current knowledge on cytokine interactions.

Humans , Animals , Female , Pregnancy , Mice , Cell Differentiation/physiology , Embryo Implantation/physiology , Embryonic Development/physiology , Endometrium/cytology , Intercellular Signaling Peptides and Proteins/physiology , Trophoblasts/cytology , Blastocyst/cytology , Blastocyst/physiology , Embryo Transfer , Endometrium/metabolism , Epidermal Growth Factor/biosynthesis , Intercellular Signaling Peptides and Proteins/metabolism , Interleukin-1/biosynthesis , Leukemia Inhibitory Factor/biosynthesis
Rev. chil. cienc. méd. biol ; 16(1): 30-38, 2006.
Article in Spanish | LILACS | ID: lil-452441


Las patologías neurodegenerativas corresponden a un grupo heterogéneo de desordenes caracterizados por cambios moleculares que desencadenan alteraciones morfológicas, asociadas a modificaciones de la conducta y disminución progresiva de la capacidad cognitiva. El notable avance en el esclarecimiento de los mecanismos moleculares implicados en la neurodegeneración, ha demostrado que existen alteraciones importantes en diversos mecanismos de transducción de señales como consecuencia de neurotoxicidad, injuria oxidativa y alteraciones moleculares en genes que codifican para proteínas claves en los mecanismos fisiológicos de aprendizaje, memoria y plasticidad neuronal. La comprensión de la fisiología y fisiopatología de estas vías de señalización, ejemplificada en la enfermedad de Alzheimer, permitiría enfocar de mejor manera el estudio de estas patologías y la búsqueda de un tratamiento efectivo para combatir estos desordenes cada vez más frecuentes debido al aumento de las expectativas de vida de la población.

Humans , Alzheimer Disease/physiopathology , Alzheimer Disease/metabolism , Neurodegenerative Diseases/physiopathology , Neurodegenerative Diseases/metabolism , Signal Transduction , Apoptosis , Intercellular Signaling Peptides and Proteins/metabolism , Receptors, Cell Surface/metabolism
Article in English | WPRIM | ID: wpr-27632


The effect of aldosterone on connective tissue growth factor (CTGF) was examined in rat embryonic ventricular myocytes. Upon aldosterone treatment, CTGF expression was significantly increased in a dose and time-dependent manner. To explore the molecular mechanism for this upregulation, we examined the role of mineralocorticoid receptor. Pre-treatment of an antagonist (spironolactone) at 5-fold excess of aldosterone blocked the CTGF induction by aldosterone, suggesting that the upregulation was mediated by mineralocorticoid receptor. Aldosterone treatment resulted in activation of ERK1/2, p38 MAPK, and JNK pathways with a more transient pat-tern in p38 MAPK. Blocking studies using pre-treatment of the inhibitor of each path-way revealed that p38 MAPK cascade may be important for aldosterone-mediated CTGF upregulation as evidenced by the blocking of CTGF induction by SB203580 (p38 MAPK inhibitor), but not by PD098059 (ERK1/2 inhibitor) and JNK inhibitor I. Interestingly, JNK inhibitor I and PD098059 decreased the basal level of CTGF expression. On the other hand, pre-treatment of spironolactone abrogated the p38 MAPK activation, indicating that mineralocorticoid receptor mechanism is linked to p38 MAPK pathway. Taken together, our findings suggest that aldosterone induces CTGF expression via both p38 MAPK cascade and mineralocorticoid receptor and that cross-talk exists between the two pathways.

Aldosterone/pharmacology , Animals , Cells, Cultured , Dose-Response Relationship, Drug , Gene Expression Regulation/drug effects , Heart Ventricles/drug effects , Immediate-Early Proteins/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Myocytes, Cardiac/drug effects , Rats , Receptors, Mineralocorticoid/metabolism , Signal Transduction/drug effects , Spironolactone/pharmacology , Up-Regulation/drug effects , p38 Mitogen-Activated Protein Kinases/metabolism
Article in Korean | WPRIM | ID: wpr-108225


BACKGROUND/AIMS: The study of liver fibrogenesis by hepatitis C virus (HCV) has been limited due to the lack of an efficiency in vitro culture systems. In the present study, we investigated whether or not HCV core protein is directly related to liver fibrogenesis through stimulation of hepatic stellate cells (HSC). METHODS: Human and rat HSC were isolated and we established an in vitro co-culture system of a stable HepG2-HCV core cell line which was transfected with HCV core gene and primary HSC. We performed immunocytochemical staining and Western and Northern blot analysis in the stimulated HSC by HCV ocre protein to identify the expression of transforming growth factor beta1 (TGF-beta1), transforming growth factor beta receptor II (TGFbeta R II), alpha-smooth muscle actin (alpha-SMA) and connective tissue growth factor (CTGF). The expression of matrix metaloprotinase-2 (MMP-2) and collagen type I (Col I) in the culture media were measured by zymogram and ELISA, respectively. RESULTS: The expression of TGF-beta1 and CTGF was significantly higher in the stable HepG2-HCV core cell line than in HepG2 cells. Furthermore, the makers related to fibrosis such as alpha-SMA, TGF-beta1, Col I, TGFRII and MMP-2 were highly experssed in the co-culture of stable HepG2-HCV core with HSC. CONCLUSIONS: HCV core protein may play a direct role in the fibrogenesis of chronic liver disease with HCV infection.

Actins/metabolism , Animals , Cell Line, Tumor , Coculture Techniques , Connective Tissue Growth Factor , Fibrosis , Hepatitis C Antigens/physiology , Humans , Immediate-Early Proteins/metabolism , Immunoblotting , Immunohistochemistry , Intercellular Signaling Peptides and Proteins/metabolism , Liver/metabolism , Protein-Serine-Threonine Kinases , Rats , Rats, Sprague-Dawley , Receptors, Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta1 , Viral Core Proteins/physiology
Article in English | WPRIM | ID: wpr-228523


Until recently, vascular endothelial growth factor (VEGF) was the only growth factor proven to be specific and critical for blood vessel formation. Other long-known factors, such as the fibroblast growth factors (FGFs), platelet-derived growth factor, or transforming growth factor-beta, had profound effects in endothelial cells. But such factors were nonspecific, in that they could act on many other cells, and it seemed unlikely that these growth factors would be effective targets for treatment of endothelial cell diseases. A recently discovered endothelial cell specific growth factor, angiopoietin, has greatly contributed to our understanding of the development, physiology, and pathology of endothelial cells (Davis et al., 1996; Yancopoulos et al., 2000). The recent studies that identified and characterized the physiological and pathological roles of angiopoietin have allowed us to widen and deepen our knowledge about blood vessel formation and vascular endothelial function. Therefore, in this review, we describe the biomedical significance of these endothelial cell growth factors, the angiopoietins, in the vascular system under normal and pathological states.

Alternative Splicing , Angiogenesis Inducing Agents/genetics , Animals , Cell Survival , Endothelial Growth Factors/metabolism , Endothelium, Vascular/cytology , Hematopoiesis/physiology , Humans , Intercellular Signaling Peptides and Proteins/metabolism , Lymphokines/metabolism , Membrane Glycoproteins/genetics , Neoplasm Proteins/metabolism , Neovascularization, Pathologic , Neovascularization, Physiologic , Signal Transduction/physiology , Urogenital System/physiology