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

Base de dados
Ano de publicação
Tipo de documento
Intervalo de ano de publicação
1.
Cell Mol Gastroenterol Hepatol ; 17(6): 887-906, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38311169

RESUMO

BACKGROUND & AIMS: Hepatic fibrosis is characterized by enhanced deposition of extracellular matrix (ECM), which results from the wound healing response to chronic, repeated injury of any etiology. Upon injury, hepatic stellate cells (HSCs) activate and secrete ECM proteins, forming scar tissue, which leads to liver dysfunction. Monocyte-chemoattractant protein-induced protein 1 (MCPIP1) possesses anti-inflammatory activity, and its overexpression reduces liver injury in septic mice. In addition, mice with liver-specific deletion of Zc3h12a develop features of primary biliary cholangitis. In this study, we investigated the role of MCPIP1 in liver fibrosis and HSC activation. METHODS: We analyzed MCPIP1 levels in patients' fibrotic livers and hepatic cells isolated from fibrotic murine livers. In vitro experiments were conducted on primary HSCs, cholangiocytes, hepatocytes, and LX-2 cells with MCPIP1 overexpression or silencing. RESULTS: MCPIP1 levels are induced in patients' fibrotic livers compared with their nonfibrotic counterparts. Murine models of fibrosis revealed that its level is increased in HSCs and hepatocytes. Moreover, hepatocytes with Mcpip1 deletion trigger HSC activation via the release of connective tissue growth factor. Overexpression of MCPIP1 in LX-2 cells inhibits their activation through the regulation of TGFB1 expression, and this phenotype is reversed upon MCPIP1 silencing. CONCLUSIONS: We demonstrated that MCPIP1 is induced in human fibrotic livers and regulates the activation of HSCs in both autocrine and paracrine manners. Our results indicate that MCPIP1 could have a potential role in the development of liver fibrosis.


Assuntos
Comunicação Autócrina , Células Estreladas do Fígado , Cirrose Hepática , Comunicação Parácrina , Ribonucleases , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Animais , Humanos , Cirrose Hepática/patologia , Cirrose Hepática/metabolismo , Camundongos , Ribonucleases/metabolismo , Ribonucleases/genética , Masculino , Modelos Animais de Doenças , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Hepatócitos/metabolismo , Hepatócitos/patologia , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Fator de Crescimento do Tecido Conjuntivo/genética , Fígado/patologia , Fígado/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA