MicroRNA-29a is a key regulon that regulates BRD4 and mitigates liver fibrosis in mice by inhibiting hepatic stellate cell activation
In: International Journal of Medical Sciences, Jg. 16 (2019), S. 212-220
Online
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Zugriff:
MicroRNA-29a is a key regulon that regulates hepatic stellate cells (HSCs) and mitigates liver fibrosis. However, the mechanism by which it does so remains largely undefined. The inhibition of bromodomain-4 protein (BRD4) represents a novel therapeutic target in hepatic fibrosis. Therefore, the purpose of this study is to investigate the miR-29a regulation of BRD4 signaling in a bile duct-ligation (BDL) animal model with regard to developing cholestatic liver fibrosis. Hepatic tissue in miR-29a transgenic mice (miR-29aTg mice) displayed weak fibrotic matrix, as shown by α-smooth muscle actin staining within affected tissues compared to wild-type mice. miR-29a overexpression reduced the BDL exaggeration of BRD4 and SNAI1 expression. Increased miR-29a signaling caused the downregulation of EZH2, MeCP2, and SNAI1, as well as the upregulation of PPAR-γ expression, in primary HSCs. We further demonstrated that the administration of JQ1, a BRD4 inhibitor, could inhibit BRD4, C-MYC, EZH2, and SNAI1 expression, while both JQ1 and a miR-29a mimic could inhibit the migration and proliferation of HSCs. In short, our research demonstrates that miR-29a negatively regulates HSC activation by inhibiting BRD4 and EZH2 function, thus making it a promising target for the pharmacologic treatment of hepatic fibrosis.
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MicroRNA-29a is a key regulon that regulates BRD4 and mitigates liver fibrosis in mice by inhibiting hepatic stellate cell activation
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Autor/in / Beteiligte Person: | Yang, Ya-Ling ; Huang, Ying-Hsien ; Kuo, Hsing-Chun ; Wang, Feng-Sheng |
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Zeitschrift: | International Journal of Medical Sciences, Jg. 16 (2019), S. 212-220 |
Veröffentlichung: | Ivyspring International Publisher, 2019 |
Medientyp: | unknown |
ISSN: | 1449-1907 (print) |
DOI: | 10.7150/ijms.29930 |
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