Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Cell Cycle ; 22(17): 1900-1920, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37603831

RESUMO

Ferroptosis is an important mode of regulated cell death (RCD). Its inhibition is closely related to therapeutic resistance and poor prognosis in hepatocellular carcinoma (HCC). Previous reports have demonstrated ferroptosis as a biological process highly dependent on selective autophagy, such as ferritinophagy, lipophagy, and clockophagy. Our study also revealed a role for ER-phagy-mediated ferroptosis in HCC cells treated with multi-targeted tyrosine kinase inhibitors (TKIs). In the current study, we found that the homologous circular RNA (circRNA) of the family with sequence similarity 134, member B (FAM134B), hsa_circ_0128505 (was abbreviated as circFAM134B in the present study), was identified to specifically target ER-phagy to promote lenvatinib (LV)-induced ferroptosis using reactive oxygen species (ROS), Fe2+, malondialdehyde (MDA), and western blot (WB) assays in HCC cells. RNA pull-down and mass spectrometry analyses suggested that circFAM134B and FAM134B mRNA were enriched with several common interacting proteins. Among them, poly (A) binding protein cytoplasmic 4 (PABPC4) was identified as the most enriched binding partner. It was proven to be a novel antagonist against the nonsense-mediated mRNA decay (NMD) mechanism. We then applied RNA immunoprecipitation (RIP), RNA pull-down, luciferase reporter, and NMD reporter gene assays to further explore the exact role and underlying mechanism of circFAM134B-PABPC4-FAM134B axis in HCC cells. circFAM134B was confirmed as a sponge that competitively interacted with PABPC4, thereby influencing FAM134B mRNA nonsense decay. Our results provide novel evidences and strategies for the comprehensive treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , MicroRNAs , Humanos , Ferroptose/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Autofagia/genética , RNA , RNA Mensageiro , Linhagem Celular Tumoral , Proliferação de Células
3.
Life Sci ; 241: 116826, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31479678

RESUMO

AIMS: Hepatitis is a kind of liver dysfunction and usually refers to a variety of pathogenic factors. Circular RNA (circRNA) participates in diverse diseases. This study aimed to explore the roles and regulatory mechanisms of the circRNA-4099 in L02 cell line. MAIN METHODS: Cells were induced with H2O2 dilutions and transfected with circRNA-4099 overproduction vectoer and the specific siRNA (si-circRNA-4099), as well as microRNA-706 (miR-706) mimic or the corresponding controls. Cell viability was detected with the CCK-8. The apoptotic rate was determined by the annexin v-FITC/PI with flow cytometer. The expression of circRNA-4099 or miR-706 was quantified depending on qRT-PCR. The reactive oxygen species (ROS) level was examined through ROS assay. The relative proteins were individually determined via western blot. The relationship between the circRNA-4099 and miR-706 was detected through bioinformatics analysis and luciferase reporter assay. KEY FINDINGS: H2O2 induced inhibition of viability and promotion of apoptosis, ROS production and cell fibrosis as well as keap1/Nrf2 and p38MAPK cascades on L02 cell line. circRNA-4099 was stimulated by H2O2. Plentiful circRNA-4099 augmented H2O2-resulted damage by inhibiting miR-706. miR-706 mimic partly abolished the influence of circRNA-4099 on L02 cells. Meanwhile, circRNA-4099 silence exerted opposite effect on these elements above. SIGNIFICANCE: circRNA-4099 aggravated H2O2-induced injury by inhibiting miR-706 through triggering keap1/Nrf2 and p38MAPK in the L02 cells.


Assuntos
Peróxido de Hidrogênio/toxicidade , Cirrose Hepática/patologia , MicroRNAs/genética , RNA Circular/genética , Linhagem Celular , Regulação para Baixo , Regulação da Expressão Gênica , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fígado/citologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
4.
Cell Biochem Funct ; 35(6): 334-338, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28845525

RESUMO

Recent evidence suggests that adventitial fibroblasts (AFs) are crucially implicated in atherosclerosis. However, the mechanisms by which AFs are dysfunctional and contribute to atherosclerosis remain unclear. This study aimed to investigate the role of regulator of G-protein signalling 3 (RGS3) in the regulation of AFs using apoE knockout mouse as the model. Pathological changes in aortic arteries of apoE knockout mice fed with hyperlipid diet were examined by Movat staining. The expression of RGS3, α-SMA, TGF-ß1, Smad2, and Smad3 in the adventitia was detected by immunohistochemistry. Adventitial fibroblasts were isolated from aortic arteries of apoE knockout mice and infected with RGS3 overexpression lentivirus or empty lentivirus. The expression of RGS3, α-SMA, TGF-ß1, Smad2, and Smad3 in AFs was detected by real-time polymerase chain reaction and Western blot analysis. We found that hyperlipidic diet caused significant aortic intima thickening and atherosclerotic plaques in 15-week-old apoE knockout mice. Compared to wild-type mice, RGS3 expression was lower while α-SMA, TGF-ß1, Smad2, and Smad3 expression was higher in the adventitia of apoE knockout mice. In addition, lentivirus mediated overexpression of RGS3 caused decreased expression of α-SMA, TGF-ß1, Smad2, and Smad3 in AFs derived from apoE(-/-) mice. In conclusion, these results suggest that RGS3 may provide protection against pathological changes of AFs and the development of atherosclerosis by inhibiting TGF-ß1/Smad signalling. RGS3 may be a potential therapeutic target for atherosclerosis.


Assuntos
Proteínas RGS/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Actinas/genética , Actinas/metabolismo , Animais , Aorta/citologia , Aorta/patologia , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Células Cultivadas , Dieta Hiperlipídica , Regulação para Baixo , Fibroblastos/citologia , Fibroblastos/metabolismo , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Imuno-Histoquímica , Lentivirus/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas RGS/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Proteína Smad2/genética , Proteína Smad3/genética , Fator de Crescimento Transformador beta1/genética
5.
Immunol Res ; 65(4): 903-912, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28612255

RESUMO

Interleukin 27 (IL-27) regulates T cell function and is involved in inflammation. It has been reported that human placenta-derived mesenchymal stromal cells (hPMSCs) can inhibit T cell responses and attenuate inflammation reactions. However, it is unclear whether IL-27 can regulate hPMSC function. Here, we examined the effects of IL-27 upon adherence, migration, and proliferation as well as the immunomodulatory effects of hPMSCs. The results show that IL-27 receptor α chain (IL-27Rα) is expressed in hPMSCs. IL-27 at 30 ng/ml inhibited hPMSC adherence and proliferation, while the migration of hPMSCs was promoted with IL-27 at doses of 20 or 30 ng/ml, as determined with use of real-time cell analysis (RTCA). Moreover, IL-27 promoted regulatory effects of hPMSCs through enhancing Th2 and suppressing Th1 subset generation from activated T cells in human peripheral blood. IL-27 also enhanced the ability of hPMSCs to secrete IL-10 from CD4+T cells through increased expression levels of the programmed death ligand 1 (PDL1) in hPMSCs via the Janus kinase (JAK)/signal transducer and activator of transcription 1 (STAT1) signaling pathway. In conclusion, IL-27 has significant modulatory effects on adherence, proliferation, and migration of hPMSCs. IL-27 increased PDL1 expression levels in hPMSCs via the JAK/STAT1 pathway, which then enhanced the regulatory effects of hPMSCs upon Th1 and Th2 cell generations and IL-10 secretion from CD4+T cells.


Assuntos
Interleucina-27/metabolismo , Células-Tronco Mesenquimais/fisiologia , Placenta/citologia , Células Th1/imunologia , Células Th2/imunologia , Antígeno B7-H1/metabolismo , Adesão Celular , Diferenciação Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Feminino , Humanos , Interleucina-10/metabolismo , Janus Quinases/metabolismo , Gravidez , Receptores de Interleucina/metabolismo , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais
6.
Int J Clin Exp Pathol ; 8(6): 6498-504, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26261527

RESUMO

Glycoprotein (transmembrane) nonmetastatic melanoma protein b (GPNMB) plays crucial roles in odontogenesis. However, the role of GPNMB in human dental pulp cells (hDPCs) is still unclear. Therefore, in this study, we investigated the expression and function of the GPNMB in odontoblastic differentiation of hDPCs. Cells were cultured in odontoblast differentiation-inducing medium; the expression of the GPNMB was assessed by reverse transcriptase polymerase chain reaction and Western blot analysis. We performed gene knockdown of GPNMB in hDPCs using lentivirus-mediated small interfering RNA (siRNA)-GPNMB. The proliferation of cells was measured by the MTT assay, and the differentiation of cells was detected with alkaline phosphatase (ALP) activity assay, qRT-PCR and Western blot were used to determine the expression levels of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1). The expression level of GPNMB was significantly increased during odontoblastic differentiation of hDPCs. Suppression of GPNMB expression by siRNA-GPNMB obviously promoted the proliferation of hDPCs. Furthermore, siRNA-GPNMB significantly inhibited the activity of ALP and expression levels of DSPP and DMP-1 during odontoblastic differentiation of hDPCs. Our results show that GPNMB plays an important role in regulating the expression of key pluripotency genes in hDPCs and modifying odontogenic differentiation.


Assuntos
Diferenciação Celular , Proliferação de Células , Polpa Dentária/metabolismo , Glicoproteínas de Membrana/metabolismo , Odontoblastos/metabolismo , Biomarcadores/metabolismo , Células Cultivadas , Polpa Dentária/citologia , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Glicoproteínas de Membrana/genética , Interferência de RNA , Transdução de Sinais , Fatores de Tempo , Transfecção
7.
J Transl Med ; 13: 38, 2015 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-25628043

RESUMO

BACKGROUND: Reactive oxide species (ROS) derived from NADPH oxidases is involved in atherosclerosis. However, as a key component of NADPH oxidase, how p47phox regulates NADPH oxidases activity, ROS production and adventitial fibroblasts (AFs) function remains unclear. METHODS: p47phox in aortic arteries of apoE(-/-) mice fed with hyperlipid diet was detected by immunohistochemistry. NADPH oxidase activity, superoxide anion (O2(-)) generation and p47phox expression were analyzed in primary AFs treated by diphenyleneiodonium (DPI). The proliferation and migration of AFs were also analyzed. RESULTS: p47phox expression was low in the aortic adventitia but high in the site of intimal injury with continuous hyperlipidic diet. Compared to AFs from wild-type mice, AFs derived from apoE(-/-) mice exhibited elevated NADPH oxidase activity, O2(-) production and higher mRNA and protein levels of p47phox, correlated with increased capability of proliferation and migration. DPI inhibited NADPH oxidase activity and AFs proliferation and migration in a dose-dependent manner. In addition, siRNA mediated knockdown of p47phox attenuated the proliferation and migration of AFs derived from apoE(-/-) mice. CONCLUSION: p47phox plays a critical role in the regulation of adventitial fibroblast proliferation and migration and may be a new therapeutic target for neointimal hyperplasia.


Assuntos
Apolipoproteínas E/fisiologia , Movimento Celular/genética , Proliferação de Células/genética , NADPH Oxidases/genética , RNA Interferente Pequeno/genética , Animais , Apolipoproteínas E/genética , Sequência de Bases , Fibroblastos/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reação em Cadeia da Polimerase Via Transcriptase Reversa
8.
Int J Clin Exp Pathol ; 8(11): 14953-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26823827

RESUMO

OBJECTIVES: Idiopathic pulmonary fibrosis (IPF) is a group of lung diseases that cause irreversible architectural distortion and impair gas, and finally progressive pulmonary functional decline and death, in which the common variant in the promoter region of the mucin 5B (MUC5B) gene may be involved. The present study aims to investigate whether variants within the MUC5B gene rs35705950 contributed to IPF susceptibility and severity in Chinese Han Population. METHODS: A total of 187 patients diagnosed with IPF and 250 healthy controls were enrolled in this study. All subjects were genotyped for MUV5B SNP rs35705950. The demographic, comorbidity, clinical and functional data were recorded. RESULTS: The rs35705950 of MUC5B were found significantly associated with increased risk of IPF susceptibility. One way ANOVA analysis found that there was a significant decreased FVC (P < 0.0001) and DLco (P < 0.0001) in correction with the minor allele of the SNP rs35705950. In the 5 years' follow-up, the carriers of the minor allele T increased mortality (P = 0.0294). CONCLUSION: This study demonstrated that the MUC5B polymorphism rs35705950 is associated with increased risk of idiopathic pulmonary fibrosis susceptibility, severity, and the decreased overall survival.


Assuntos
Predisposição Genética para Doença/genética , Fibrose Pulmonar Idiopática/genética , Mucina-5B/genética , Polimorfismo de Nucleotídeo Único , Idoso , Povo Asiático/genética , Feminino , Genótipo , Humanos , Fibrose Pulmonar Idiopática/mortalidade , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais
9.
Mol Immunol ; 48(9-10): 1203-8, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21466895

RESUMO

Hepatitis B virus (HBV)-induced hepatic inflammation afflicts hundreds of millions of people worldwide and is a leading cause of hepatic cancer. While the deleterious effect of the chronic hepatitis is well recognized, the molecular mechanisms underlying the pathogenesis of HBV-induced hepatic inflammation are not well understood. We report here that the tumor necrosis factor-alpha-induced protein-8 like-2 (TIPE2 or TNFAIP8L2), a newly identified regulator of immune receptor signaling, plays an important role in controlling HBV-induced hepatitis. Patients with chronic hepatitis B had significantly reduced levels of TIPE2 expression in their peripheral blood mononuclear cells (PBMCs) as compared to healthy individuals. The TIPE2 expression negatively correlated with the blood levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (Tbil) as well as the HBV load of the patients. Importantly, using a murine model of HBV-induced hepatitis, we found that TIPE2-deficient mice developed significantly more severe hepatic inflammation than wild type mice. These results indicate that TIPE2 plays an important role in taming HBV-induced hepatic inflammation.


Assuntos
Vírus da Hepatite B/fisiologia , Hepatite B Crônica/virologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fígado/patologia , Fígado/virologia , Adolescente , Adulto , Animais , Estudos de Casos e Controles , Criança , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Hepatite B Crônica/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Peptídeos e Proteínas de Sinalização Intracelular/genética , Leucócitos Mononucleares/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...