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PLoS One. 2019 Jun 5;14(6):e0214534. doi: 10.1371/journal.pone.0214534. eCollection 2019.

TGF-β induces liver fibrosis via miRNA-181a-mediated down regulation of augmenter of liver regeneration in hepatic stellate cells.

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Faculty of Life Sciences and Biotechnology, South Asian University, Akbar Bhawan, Chanakyapuri, New Delhi, India.
Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.



To study the role of miRNA-181a and augmenter of liver regeneration in TGF-β-induced fibrosis in hepatic stellate cells.


LX2 cells were treated with 20 ng/ml TGF-β for 24 h. miRNA-181a, ALR plasmid and empty vectors were transfected using siPORT NeoFx reagent. Cells were harvested after 48 h or 72 h of transfection for protein or RNA analysis. Western blotting was performed for ALR, TGF-β receptor II (TGFβ-RII), collagen 1A1 (COLL1A1), alpha-smooth muscle cell actin (α-SMA), rac1, E-cadherin and β-actin. Quantitative RT-PCR was performed for ALR, GAPDH, miRNA-181a or 5S rRNA.


TGF-β induced the expression of miRNA-181a, which in turn down-regulated ALR thereby induced the fibrosis markers, such as COLL1A1, α-SMA and rac1 in hepatic stellate cells. Over-expression of miRNA-181a down-regulated expression of ALR and up-regulated expression of fibrosis markers. On the other hand, ALR over-expression resulted in a decrease in miRNA-181a expression and fibrosis markers. Over-expression of ALR also inhibited the expression of TGFβ-RII and increased expression E-cadherin.


TGF-β induced miRNA-181a, which in turn induced fibrosis, at least in part, by inhibiting ALR. ALR inhibited TGF-β action by decreasing the expression of TGFβ-RII, thereby inhibiting miRNA-181a expression and fibrosis markers. ALR could serve as a potential molecule to inhibit liver fibrosis.

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