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1.
Palliat Support Care ; : 1-12, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38533614

RESUMO

OBJECTIVES: We determined the validity and reliability of the Spanish translation Sheffield Profile for Assessment and Referral for Care (SPARC-Sp) questionnaire to identify the palliative care (PC) needs of patients with chronic noncommunicable diseases (NCDs) in Colombia. METHODS: We developed a cross-sectional observational study of scale assessment in adults with the aim of determining the validity and reliability of the SPARC-Sp questionnaire to identify the PC needs of patients with NCDs receiving outpatient or inpatient care at the Hospital Universitario San Jose of Popayan - ESE, Colombia, from 2021 to 2022. RESULTS: We applied a questionnaire consisting of demographic, clinical data, and SPARC-Sp to 507 participants. The constructed model explained 75% of the variance with an adequate fit according to the root mean square residual (0.03), the comparative fit index (0.98), and acceptable reliability (McDonald's total omega 0.4-0.9). Opportunities for improvement are the reformulation and inclusion of particular words to improve the representativeness and clarity of the domains of communication and information, religious, and spiritual issues. SIGNIFICANCE OF RESULTS: This research represents the first validation of SPARC in Spanish. SPARC-Sp is an instrument that allows initiating a conversation of the patient's main needs through a systematic assessment of the patients' main needs. Its psychometric validation demonstrated good fit and acceptable reliability.

2.
J Physiol Biochem ; 79(4): 815-831, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36018492

RESUMO

Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix glycoprotein with pleiotropic functions, which is expressed in adipose, hepatic, muscular, and pancreatic tissue. Particularly, several studies demonstrated that SPARC is an important player in the context of obesity, diabetes, and fatty liver disease including advanced hepatic fibrosis and hepatocellular carcinoma. Evidence in murine and human samples indicates that SPARC is involved in adipogenesis, cellular metabolism, extracellular matrix modulation, glucose and lipid metabolism, among others. Furthermore, studies in SPARC knockout mouse model showed that SPARC contributes to adipose tissue formation, non-alcoholic fatty liver disease (NAFLD), and diabetes. Hence, SPARC may represent a novel and interesting target protein for future therapeutic interventions or a biomarker of disease progression. This review summarizes the role of SPARC in the pathophysiology of obesity, and extensively revised SPARC functions in physiological and pathological adipose tissue deposition, muscle metabolism, liver, and diabetes-related pathways.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Camundongos , Humanos , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Osteonectina/genética , Osteonectina/metabolismo , Cisteína , Diabetes Mellitus Tipo 2/complicações , Obesidade/metabolismo , Camundongos Knockout
3.
Int J Mol Sci ; 23(11)2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35682554

RESUMO

Secreted protein acidic and rich in cysteine (SPARC), or osteonectin, is a matricellular protein that modulates interactions between cells and their microenvironment. SPARC is expressed during extracellular matrix remodeling and is abundant in bone marrow and high-grade prostate cancer (PCa). In PCa, SPARC induces changes associated with epithelial-mesenchymal transition (EMT), enhancing migration and invasion and increasing the expression of EMT transcriptional factor Zinc finger E-box-binding homeobox 1 (ZEB1), but not Zinc finger protein SNAI1 (Snail) or Zinc finger protein SNAI2 (Slug). It is unknown whether the SPARC-induced downregulation of E-cadherin in PCa cells depends on ZEB1. Several integrins are mediators of SPARC effects in cancer cells. Because integrin signaling can induce EMT programs, we hypothesize that SPARC induces E-cadherin repression through the activation of integrins and ZEB1. Through stable knockdown and the overexpression of SPARC in PCa cells, we demonstrate that SPARC downregulates E-cadherin and increases vimentin, ZEB1, and integrin ß3 expression. Knocking down SPARC in PCa cells decreases the tyrosine-925 phosphorylation of FAK and impairs focal adhesion formation. Blocking integrin αvß3 and silencing ZEB1 revert both the SPARC-induced downregulation of E-cadherin and cell migration enhancement. We conclude that SPARC induces E-cadherin repression and enhances PCa cell migration through the integrin αvß3/ZEB1 signaling pathway.


Assuntos
Neoplasias da Próstata , Fatores de Transcrição , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Humanos , Integrina alfaVbeta3/metabolismo , Masculino , Invasividade Neoplásica , Osteonectina/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Microambiente Tumoral , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo
4.
Front Genet ; 12: 788346, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899866

RESUMO

While cartilage is an ancient tissue found both in protostomes and deuterostomes, its mineralization evolved more recently, within the vertebrate lineage. SPARC, SPARC-L, and the SCPP members (Secretory Calcium-binding PhosphoProtein genes which evolved from SPARC-L) are major players of dentine and bone mineralization, but their involvement in the emergence of the vertebrate mineralized cartilage remains unclear. We performed in situ hybridization on mineralizing cartilaginous skeletal elements of the frog Xenopus tropicalis (Xt) and the shark Scyliorhinus canicula (Sc) to examine the expression of SPARC (present in both species), SPARC-L (present in Sc only) and the SCPP members (present in Xt only). We show that while mineralizing cartilage expresses SPARC (but not SPARC-L) in Sc, it expresses the SCPP genes (but not SPARC) in Xt, and propose two possible evolutionary scenarios to explain these opposite expression patterns. In spite of these genetic divergences, our data draw the attention on an overlooked and evolutionarily conserved peripheral cartilage subdomain expressing SPARC or the SCPP genes and exhibiting a high propensity to mineralize.

5.
Immunobiology ; 226(3): 152095, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34000572

RESUMO

BACKGROUND: Ulcerative colitis (UC) is an inflammatory disease of the intestine. The genetics factors play an important role in the pathogenesis of UC. SPARC exacerbates colonic inflammatory symptoms in dextran sodium sulphate-induced murine colitis. The aim of the study was to measure the gene expression and intestinal production of SPARC in patients with UC and controls as well as, to determine its correlation with histological activity. METHODS: We included 40 patients with confirmed diagnosis of UC, and 20 controls without endoscopic evidence of any type of colitis or neoplasia. The relative quantification of the gene expression was performed by real time PCR. GAPDH was used as housekeeping gene for normalization purposes and quality controls. Protein expression was determined by immunohistochemistry. RESULTS: The gene expression of SPARC was increased in patients with active UC vs in remission UC and vs. controls (P = 0.005). There was no significant difference between patients with remission UC and controls. The overexpression of SPARC in patients with active UC correlated significantly with mild histological activity (P = 0.06, OR = 7.77, IC = 0.77-77.9) moderate (P = 0.06, OR = 8.1, IC 95%=0.79-82.73), and severe (P = 0.03, OR = 6.5, IC 95%=1.09-38.6). Double positive SPARC+/CD16+ cells were localized mainly in submucosa, muscular layer, and adventitia, and in perivascular inflammatory infiltrates in patients with active UC. CONCLUSION: The gene and protein expression of SPARC is increased in active UC. SPARC could be a marker of intestinal inflammation and its expression correlates with histological activity.


Assuntos
Colite Ulcerativa/etiologia , Colite Ulcerativa/metabolismo , Mucosa Intestinal/metabolismo , Osteonectina/biossíntese , Adulto , Idoso , Biomarcadores , Colite Ulcerativa/diagnóstico , Estudos Transversais , Suscetibilidade a Doenças , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Osteonectina/genética , Adulto Jovem
6.
Mol Cell Endocrinol ; 530: 111253, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33781836

RESUMO

Parathyroid hormone-related peptide (PTHrP) exerts its effects on cells derived from colorectal cancer (CRC) and tumor microenvironment and is involved in processes requiring the epithelial-mesenchymal transition (EMT). Here, we report that PTHrP modulates factors expression and morphological changes associated with EMT in HCT116 cells from CRC. PTHrP increased the protein expression of SPARC, a factor involved in EMT, in HCT116 cells but not in Caco-2 cells also from CRC but with less aggressiveness. PTHrP also increased SPARC expression and its subsequent release from endothelial HMEC-1 cells. The conditioned media of PTHrP-treated HMEC-1 cells induced early changes related to EMT in HCT116 cells. Moreover, SPARC treatment on HCT116 cells potentiated PTHrP modulation in E-cadherin expression and cell migration. In vivo PTHrP also increased SPARC expression and decreased E-cadherin expression. These results suggest a novel PTHrP action on CRC progression involving the microenvironment in the modulation of events associated with EMT.


Assuntos
Antígenos CD/metabolismo , Caderinas/metabolismo , Neoplasias do Colo/patologia , Células Endoteliais/citologia , Osteonectina/metabolismo , Proteína Relacionada ao Hormônio Paratireóideo/metabolismo , Regulação para Cima , Animais , Células CACO-2 , Linhagem Celular , Movimento Celular , Proliferação de Células , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Meios de Cultivo Condicionados/química , Progressão da Doença , Células Endoteliais/metabolismo , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Camundongos , Transplante de Neoplasias , Osteonectina/genética , Proteína Relacionada ao Hormônio Paratireóideo/genética , Microambiente Tumoral
7.
Glia ; 69(6): 1429-1443, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33497496

RESUMO

Central nervous system (CNS) function depends on precise synaptogenesis, which is shaped by environmental cues and cellular interactions. Astrocytes are outstanding regulators of synapse development and plasticity through contact-dependent signals and through the release of pro- and antisynaptogenic factors. Conversely, myelin and its associated proteins, including Nogo-A, affect synapses in a inhibitory fashion and contribute to neural circuitry stabilization. However, the roles of Nogo-A-astrocyte interactions and their implications in synapse development and plasticity have not been characterized. Therefore, we aimed to investigate whether Nogo-A affects the capacity of astrocytes to induce synaptogenesis. Additionally, we assessed whether downregulation of Nogo-A signaling in an in vivo demyelination model impacts the synaptogenic potential of astrocytes. Our in vitro data show that cortical astrocytes respond to Nogo-A through RhoA pathway activation, exhibiting stress fiber formation and decreased ramified morphology. This phenotype was associated with reduced levels of GLAST protein and aspartate uptake, decreased mRNA levels of the synaptogenesis-associated genes Hevin, glypican-4, TGF-ß1 and BDNF, and decreased and increased protein levels of Hevin and SPARC, respectively. Corroborating these findings, conditioned medium from Nogo-A-treated astrocytes suppressed the formation of structurally and functionally mature synapses in cortical neuronal cultures. After cuprizone-induced acute demyelination, we observed reduced immunostaining for Nogo-A in the visual cortex accompanied by higher levels of Hevin expression in astrocytes and an increase in excitatory synapse density. Hence, we suggest that interactions between Nogo-A and astrocytes might represent an important pathway of plasticity regulation and could be a target for therapeutic intervention in demyelinating diseases in the future.


Assuntos
Astrócitos , Doenças Desmielinizantes , Humanos , Neurogênese , Proteínas Nogo , Sinapses
8.
Oncotarget ; 10(41): 4169-4179, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31289615

RESUMO

SPARC, also known as osteonectin and BM-40, is a matricellular protein with a number of biological functions. Hepatic SPARC expression is induced in response to thioacetamide, bile-duct ligation, and acute injuries such as concanavalin A and lipopolysacharide (LPS)/D-galactosamine. We have previously demonstrated that the therapeutic inhibition of SPARC or SPARC gene deletion protected mice against liver injury. We investigated the mechanisms involved in the protective effect of SPARC inhibition in mice. We performed a proteome analysis of livers from SPARC+/+ and SPARC-/- mice chronically treated with thioacetamide. Catalase activity, carbonylation levels, oxidative stress response, and mitochondrial function were studied. Genomic analysis revealed that SPARC-/- mice had an increased expression of cell proliferation genes. Proteins involved in detoxification of reactive oxygen species such as catalase, peroxirredoxine-1, and glutathione-S-transferase P1 and Mu1 were highly expressed as evidenced by proteome analysis; hepatic catalase activity was increased in SPARC-/- mice. Oxidative stress response and carbonylation levels were lower in livers from SPARC-/- mice. Hepatic mitochondria showed lower levels of nitrogen reactive species in the SPARC-/- concanavalin A-treated mice. Mitochondrial morphology was preserved, and its complex activity reduced in SPARC-/- mice. In conclusion, our data suggest that the protection associated with SPARC gene deletion may be partially due to a higher proliferative capacity of hepatocytes and an enhanced oxidative stress defense in SPARC-/- mice after liver injury.

9.
Asian J Androl ; 21(6): 557-564, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31031331

RESUMO

Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein highly expressed in bone tissue that acts as a chemoattractant factor promoting the arrival of prostate cancer (PCa) cells to the bone marrow. However, the contribution of SPARC during the early stages of tumor progression remains unclear. In this study, we show that SPARC is highly expressed in PCa tissues with a higher Gleason score. Through stable knockdown and overexpression of SPARC in PC3 and LNCaP cells, respectively, here we demonstrate that endogenous SPARC induces the epithelial-mesenchymal transition (EMT), decreasing E-cadherin and cytokeratin 18 and increasing N-cadherin and vimentin. Moreover, SPARC induces the expression of EMT regulatory transcription factors Snail family transcriptional repressor 1 (Snail), Snail family transcriptional repressor 2 (Slug), and zinc finger E-box binding homeobox 1 (Zeb1). In addition, SPARC knockdown in PC3 cells decreases migration and invasion in vitro, without modifying cell proliferation. Our results indicate that SPARC might facilitate tumor progression by modifying the cellular phenotype in cancer cells.


Assuntos
Transição Epitelial-Mesenquimal , Osteonectina/metabolismo , Neoplasias da Próstata/patologia , Western Blotting , Linhagem Celular Tumoral , Humanos , Masculino , Gradação de Tumores , Invasividade Neoplásica , Neoplasias da Próstata/metabolismo , Análise Serial de Tecidos
10.
Clin Sci (Lond) ; 133(2): 351-365, 2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30626728

RESUMO

Obesity, metabolic syndrome, and type 2 diabetes, three strongly interrelated diseases, are associated to increased morbidity and mortality worldwide. The pathogenesis of obesity-associated disorders is still under study. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein expressed in many cell types including adipocytes, parenchymal, and non-parenchymal hepatic cells and pancreatic cells. Studies have demonstrated that SPARC inhibits adipogenesis and promotes insulin resistance; in addition, circulating SPARC levels were positively correlated with body mass index in obese individuals. Therefore, SPARC is being proposed as a key factor in the pathogenesis of obesity-associated disorders. The aim of this study is to elucidate the role of SPARC in glucose homeostasis. We show here that SPARC null (SPARC-/-) mice displayed an abnormal insulin-regulated glucose metabolism. SPARC-/- mice presented an increased adipose tissue deposition and an impaired glucose homeostasis as animals aged. In addition, the absence of SPARC worsens high-fat diet-induced diabetes in mice. Interestingly, although SPARC-/- mice on high-fat diet were sensitive to insulin they showed an impaired insulin secretion capacity. Of note, the expression of glucose transporter 2 in islets of SPARC-/- mice was dramatically reduced. The present study provides the first evidence that deleted SPARC expression causes diabetes in mice. Thus, SPARC deficient mice constitute a valuable model for studies concerning obesity and its related metabolic complications, including diabetes.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Insulina/sangue , Ilhotas Pancreáticas/metabolismo , Osteonectina/metabolismo , Envelhecimento/sangue , Animais , Biomarcadores/sangue , Diabetes Mellitus Experimental/genética , Dieta Hiperlipídica , Sacarose Alimentar , Transportador de Glucose Tipo 2/metabolismo , Homeostase , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteonectina/deficiência , Osteonectina/genética , Via Secretória
11.
Reprod Biol Endocrinol ; 16(1): 116, 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30424792

RESUMO

BACKGROUND: Matrix metalloproteinases (Mmps) and their tissue inhibitors (Timps) are widely recognized as crucial factors for extracellular matrix remodeling in the ovary and are involved in follicular growth, ovulation, luteinization, and luteolysis during the estrous cycle. Recently, several genes have been associated to the modulation of Mmps activity, including Basigin (Bsg), which induces the expression of Mmps in rat ovaries; Sparc, a TGF-ß modulator that is related to increased expression of Mmps in cancer; and Reck, which is associated with Mmps inhibition. However, the expression pattern of Mmp modulators in ovary dynamics is still largely uncharacterized. METHODS: To characterize the expression pattern of Mmps network members in ovary dynamics, we analyzed the spatio-temporal expression pattern of Reck and Sparc, as well as of Mmp2, Mmp9 and Mmp14 proteins, by immunohistochemistry (IHC), in pre-pubertal rat ovaries obtained from an artificial cycle induced by eCG/hCG, in the different phases of the hormone-induced estrous cycle. We also determined the gene expression profiles of Mmps (2, 9, 13 14), Timps (1, 2, 3), Sparc, Bsg, and Reck to complement this panel. RESULTS: IHC analysis revealed that Mmp protein expression peaks at the early stages of folliculogenesis and ovulation, decreases during ovulation-luteogenesis transition and luteogenesis, increasing again during corpus luteum maintenance and luteolysis. The protein expression patterns of these metalloproteinases and Sparc were inverse relative to the pattern displayed by Reck. We observed that the gene expression peaks of Mmps inhibitors Reck and Timp2 were closely paraleled by Mmp2 and Mmp9 suppression. The opposite was also true: increased Mmp2 and Mmp9 expression was concomitant to reduced Reck and Timp2 levels. CONCLUSION: Therefore, our results generate a spatio-temporal expression profile panel of Mmps and their regulators, suggesting that Reck and Sparc seem to play a role during ovarian dynamics: Reck as a possible inhibitor and Sparc as an inducer of Mmps.


Assuntos
Perfilação da Expressão Gênica , Osteonectina/genética , Ovário/metabolismo , Proteínas Supressoras de Tumor/genética , Animais , Basigina/genética , Basigina/metabolismo , Proteínas Sanguíneas/genética , Proteínas Sanguíneas/metabolismo , Ciclo Estral/genética , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Osteonectina/metabolismo , Ovulação/genética , Ratos Sprague-Dawley , Maturidade Sexual/genética , Fatores de Tempo , Inibidores Teciduais de Metaloproteinases/genética , Inibidores Teciduais de Metaloproteinases/metabolismo , Proteínas Supressoras de Tumor/metabolismo
12.
Genes Brain Behav ; 11(8): 966-76, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22950524

RESUMO

SPARC (secreted protein acidic and rich in cysteine) is a matricellular protein highly expressed during development, reorganization and tissue repair. In the central nervous system, glial cells express SPARC during development and in neurogenic regions of the adult brain. Astrocytes control the glutamate receptor levels in the developing hippocampus through SPARC secretion. To further characterize the role of SPARC in the brain, we analyzed the hippocampal-dependent adult behavior of SPARC KO mice. We found that SPARC KO mice show increased levels of anxiety-related behaviors and reduced levels of depression-related behaviors. The antidepressant-like phenotype could be rescued by adenoviral vector-mediated expression of SPARC in the adult hippocampus, but anxiety-related behavior persisted in these mice. To identify the cellular mechanisms underlying these behavioral alterations, we analyzed neuronal activity and neurogenesis in the dentate gyrus (DG). SPARC KO mice have increased levels of neuronal activity, evidenced as more neurons that express c-Fos after a footshock. SPARC also affects cell proliferation in the subgranular zone of the DG, although it does not affect maturation and survival of new neurons. SPARC expression in the adult DG does not revert the proliferation phenotype in KO mice, but our results suggest a role of SPARC in limiting the survival of new neurons in the DG. This work suggests that SPARC could affect anxiety-related behavior by modulating neuronal activity, and that depression-related behavior is dependent upon the adult expression of SPARC, which affects adult brain function by mechanisms that need to be elucidated.


Assuntos
Depressão/genética , Hipocampo/fisiopatologia , Osteonectina/genética , Fatores Etários , Animais , Ansiedade/genética , Ansiedade/fisiopatologia , Proliferação de Células , Giro Denteado/fisiopatologia , Depressão/fisiopatologia , Feminino , Masculino , Camundongos , Camundongos Knockout , Neurogênese/genética , Fenótipo
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