Reversibility and heritability of liver fibrosis: Implications for research and therapy

Table 3 Summary of recent studies evaluating role of miRNA in liver fibrosis

miRNA	Function	Ref.
miR-15b/16	Downregulated in aHSCs. Restoring miR-16 and miR-15b reduced Bcl-2, and increased expression of caspases 3, 8, and 9 and aHSC apoptosis	Guo et al[87]
miR-19b	Downregulated in aHSCs and in human fibrotic liver. miR-19b binds to the 3'-UTR of TGF-βRII. miR-19b mimic decreases expression of TGF-βRII, collagen and α-SMA and increases quiescent characteristics	Lakner et al[44]
miR-21	Upregulated in PDGF-BB-aHSCs through PTEN/Akt pathway	Wei et al[88]
miR-21	Upregulated in cirrhotic patients and rats. Targets the 3'-UTR of SPRY2 and HNF4α mRNAs in human and rat. Downregulating miR-21 suppressed ERK1 signaling, inhibited HSC activation, and blocked EMT in TGFβ1-treated hepatocytes	Zhao et al[45]
miR-27a/b	Upregulated in cultured-aHSCs. Downregulation of miR-27a/b induced quiesent HSC phenotype. Target Retinoid X receptor α (RXRα)	Ji et al[46]
miR-29a/b/c	Decreased expression in murine and human fibrotic livers. Serum expression negatively correlated with degree of liver fibrosis in humans	Roderburg et al[48]
miR-29b	miR-29b overexpression suppressed Col1α1 mRNA and protein	Ogawa et al[43]
miR-29b	Downregulated during HSC activation in primary culture. miR-29 overexpression attenuated the increased expression of Col1α1 and Col1α2, α-SMA, DDR2, FN1, ITGB1, and PDGFR-β mRNAs, inhibited HSC activation and supressed c-fos mRNA	Sekiya et al[47]
miR-122	Downregulated in HCV-induced liver fibrosis. Expression inversly correlated with fibrosis stage	Morita et al[89]
miR-132	Downregulated in aHSCs. In quiescent HSCs miR-132 binds and represses MeCP2 transcripts that carry an extended 3'-UTR that includes the miR132 recognition motif. MeCP promotes methylation of H3K27 of PPARγ through stimulation of EZH2	Mann et al[16]
miR-150, miR-194	Both are reduced in aHScs. miR-150 targets c-myb and miR-194 targets rac-1. Both inhibit HSC activation and ECM production via inhibition of c-myb and rac-1	Venugopal et al[90]
miR-155	Decreased expression in aHSCs, sera and liver tissues of cirrhotic patients. MiR-155 interacts with 3'-UTR of TCF4 and AGTR1 mRNAs involved in EMT and ERK1 pathway, repectively	Dai et al[50]
miR-199/200	Expression correlated to progression of liver fibrosis	Murakami et al[91]
miR-214-5p	Upregulated in human and mouse fibrotic liver	Iizuka et al[92]
miR-221/222	Upregulated in human liver in a fibrosis progression-dependent manner	Ogawa et al[93]
miR-335	Downregulated during HSC activation. Restoring expression of miR-335 inhibited HSC migration and reduced α-SMA and collagen type I	Chen et al[94]

HSC: Hepatic stellate cell; 3'-UTR: 3'-Untranslated region.