Gli3 is a novel downstream target of miR‑200a with an anti‑fibrotic role for progression of liver fibrosis in�vivo and in�vitro

Abstract

GLI family zinc finger 3 (Gli3), as the upstream transcriptional activator of hedgehog signaling, has previously been demonstrated to participate in the process of liver fibrosis. The present study aimed to investigate the potential functions of microRNA (miR)-200a and Gli3 in the progression of liver fibrosis. The expression levels of miR-200a and Gli3 in cells and tissues were determined by PCR and western blotting; the interaction of Gli3 and miR-200a was evaluated by bioinformatics analysis and dual-luciferase reporter assay. miR-200a was significantly reduced in serum samples from clinical patients, liver tissues of a carbon tetrachloride (CCl 4)-induced rat model and activated LX2 cells. The expression of α-smooth muscle actin (α-SMA) and albumin at the mRNA and protein levels was increased and decreased in LX2 cells, respectively. However, the expression levels of α-SMa and albumin were reversed and Gli3 expression was markedly decreased in LX2 cells when transfected with miR-200a mimics. In addition, the dual-luciferase reporter assay confirmed the target interaction between miR-200a and Gli3. Finally, following the administration of miR-200a mimics to CCl 4-induced rats, it was revealed that the alterations of α-SMA, albumin and Gli3 presented a similar trend to that in LX2 cells with miR-200a mimics transfection. Taken together, these results indicated that downregulation of miR-200a might enhance the formation of liver fibrosis, probably by targeting Gli3, and elevated miR-200a may attenuate the progression of liver fibrosis by suppressing Gli3. These findings suggested that miR-200a may function as a novel anti-fibrotic agent in liver fibrosis via inhibition of the expression of Gli3.

MicroRNA 200a inhibits liver fibrosis of schistosoma

“…In addition, the level of IL-4 in the Lenti-miR-200a group decreased significantly in the 4th and 8th weeks of infection, suggesting that miR-200a could inhibit the development of liver fibrosis to some extent. It has been reported that increasing expression of miR-200a attenuates HSC proliferation while knocking down miR-200a-promoted HSC proliferation [ 21 ]. And consistent with our result, it was reported that miR-200a upregulation contributed to the suppression of activated HSCs, leading to a reduction in cell proliferation, ECM production and α-SMA expression [ 22 , 23 ].…”