Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 23, Issue 6, Pages 3824-3832Publisher
WILEY
DOI: 10.1111/jcmm.14210
Keywords
HSC activation; liver fibrosis; miR-13b-3p; miR-193a-3p
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Funding
- National Natural Science Foundation of China [81270513, 81700544]
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MicroRNAs (miRNAs) have been confirmed to participate in liver fibrosis progression and activation of hepatic stellate cells (HSCs). In this study, the role of miR-193a/b-3p in concanavalin A (ConA)-induced liver fibrosis in mice was evaluated. According to the results, the expression of miR-193a/b-3p was down-regulated in liver tissues after exposure to ConA. Lentivirus-mediated overexpression of miR-193a/b-3p reduced ConA-induced liver injury as demonstrated by decreasing ALT and AST levels. Moreover, ConA-induced liver fibrosis was restrained by the up-regulation of miR-193a/b-3 through inhibiting collagen deposition, decreasing desmin and proliferating cell nuclear antigen (PCNA) expression and lessening the content of hydroxyproline, transforming growth factor-beta 1 (TGF-beta 1) and activin A in liver tissues. Furthermore, miR-193a/b-3p mimics suppressed the proliferation of human HSCs LX-2 via inducing the apoptosis of LX-2 cells and lowering the levels of cell cycle-related proteins Cyclin D1, Cyclin E1, p-Rb and CAPRIN1. Finally, TGF-beta 1 and activin A-mediated activation of LX-2 cells was reversed by miR-193a/b-3p mimics via repressing COL1A1 and beta-SMA expression, and restraining the activation of TGF-beta/Smad2/3 signalling pathway. CAPRIN1 and TGF-beta 2 were demonstrated to be the direct target genes of miR-193a/b-3p. We conclude that miR-193a/b-3p overexpression attenuates liver fibrosis through suppressing the proliferation and activation of HSCs. Our data suggest that miR-193a-3p and miR-193b-3p may be new therapeutic targets for liver fibrosis.
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