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10.1111/jcmm.12655

http://scihub22266oqcxt.onion/10.1111/jcmm.12655
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suck abstract from ncbi


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pmid26257392
      J+Cell+Mol+Med 2015 ; 19 (11 ): 2617-32
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  • Salvianolic acid B-induced microRNA-152 inhibits liver fibrosis by attenuating DNMT1-mediated Patched1 methylation #MMPMID26257392
  • Yu F ; Lu Z ; Chen B ; Wu X ; Dong P ; Zheng J
  • J Cell Mol Med 2015[Nov]; 19 (11 ): 2617-32 PMID26257392 show ga
  • Epithelial-mesenchymal transition (EMT) was reported to be involved in the activation of hepatic stellate cells (HSCs), contributing to the development of liver fibrosis. Epithelial-mesenchymal transition can be promoted by the Hedgehog (Hh) pathway. Patched1 (PTCH1), a negative regulatory factor of the Hh signalling pathway, was down-regulated during liver fibrosis and associated with its hypermethylation status. MicroRNAs (miRNAs) are reported to play a critical role in the control of various HSCs functions. However, miRNA-mediated epigenetic regulations in EMT during liver fibrosis are seldom studied. In this study, Salvianolic acid B (Sal B) suppressed the activation of HSCs in CCl4 -treated mice and mouse primary HSCs, leading to inhibition of cell proliferation, type I collagen and alpha-smooth muscle actin. We demonstrated that the antifibrotic effects caused by Sal B were, at least in part, via inhibition of EMT and the Hh pathway. In particular, up-regulation of PTCH1 was associated with decreased DNA methylation level after Sal B treatment. Accordingly, DNA methyltransferase 1 (DNMT1) was attenuated by Sal B in vivo and in vitro. The knockdown of DNMT1 in Sal B-treated HSCs enhanced PTCH1 expression and its demethylation level. Interestingly, increased miR-152 in Sal B-treated cells was responsible for the hypomethylation of PTCH1 by Sal B. As confirmed by the luciferase activity assay, DNMT1 was a direct target of miR-152. Further studies showed that the miR-152 inhibitor reversed Sal B-mediated PTCH1 up-regulation and DNMT1 down-regulation. Collectively, miR-152 induced by Sal B, contributed to DNMT1 down-regulation and epigenetically regulated PTCH1, resulting in the inhibition of EMT in liver fibrosis.
  • |Animals [MESH]
  • |Benzofurans/pharmacology/*therapeutic use [MESH]
  • |Epigenesis, Genetic [MESH]
  • |Liver Cirrhosis/genetics/metabolism/*therapy [MESH]
  • |Methylation/drug effects [MESH]
  • |Mice [MESH]
  • |MicroRNAs/genetics/*metabolism [MESH]
  • |Patched-1 Receptor/*metabolism [MESH]


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