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MicroRNA-489-3p Represses Hepatic Stellate Cells Activation by Negatively Regulating the JAG1/Notch3 Signaling Pathway.
Li, Juanjuan; Dong, Shouquan; Ye, Mingliang; Peng, Ganjing; Luo, Jie; Wang, Chun; Wang, Jing; Zhao, Qiu; Chang, Ying; Wang, Hongling.
Afiliación
  • Li J; Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, Hubei, China.
  • Dong S; Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, Hubei, China.
  • Ye M; Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, Hubei, China.
  • Peng G; Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, Hubei, China.
  • Luo J; Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, Hubei, China.
  • Wang C; Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, Hubei, China.
  • Wang J; Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, Hubei, China.
  • Zhao Q; Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, Hubei, China.
  • Chang Y; Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, Hubei, China.
  • Wang H; Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, Hubei, China. zhnwhl@whu.edu.cn.
Dig Dis Sci ; 66(1): 143-150, 2021 01.
Article en En | MEDLINE | ID: mdl-32144602
BACKGROUND: The transformation of hepatic stellate cells (HSCs) into collagen-producing myofibroblasts is a key event in hepatic fibrogenesis. Recent studies have shown that microRNAs (miRNAs) play a critical role in the transformation of HSCs. However, the function of miR-489-3p in liver fibrosis remains unclear. METHODS: Here, we detected the levels of miR-489-3p and jagged canonical Notch ligand 1 (JAG1) in liver fibrosis by using CCl4-treated rats as an in vivo model and transforming growth factor-beta 1 (TGF-ß1)-treated HSC cell lines LX-2 and HSC-T6 as in vitro models. The expression of profibrotic markers was affected by transfecting LX-2 cells with either miR-489-3p mimic or si-JAG1. A dual-luciferase reporter assay was carried out to study the interaction of JAG1 with miR-489-3p. RESULTS: We found that miR-489-3p was remarkably decreased while JAG1 was increased in liver fibrosis models both in vivo and in vitro. Overexpression of miR-489-3p reduced the expression of profibrotic markers and the activation of LX-2 cells induced by TGF-ß1. Moreover, miR-489-3p decreased the expression of jagged canonical Notch ligand 1 (JAG1) in LX-2 cells by interacting with its 3'-UTR. As JAG1 is a Notch ligand, decreased JAG1 by miR-489-3p inhibited the Notch signaling pathway. Moreover, the downregulation of JAG1 inhibited the expression of fibrotic markers. CONCLUSION: Our results indicate that miR-489-3p can inhibit HSC activation by inhibiting the JAG1/Notch3 signaling pathway.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / MicroARNs / Células Estrelladas Hepáticas / Proteína Jagged-1 / Receptor Notch3 / Cirrosis Hepática Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Dig Dis Sci Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / MicroARNs / Células Estrelladas Hepáticas / Proteína Jagged-1 / Receptor Notch3 / Cirrosis Hepática Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Dig Dis Sci Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos