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

Aim Hepatocytes can proliferate and regenerate when injured by toxins, viral infections, and so on. Augmenter of liver regeneration (ALR) is a key regulator of liver regeneration, but the mechanism is unknown. The role of ALR in other cell types is not known. In the present study, we investigated the relationship between microRNA (miRNA)‐26a and ALR in the Huh7 cell line and adipose tissue‐derived mesenchymal cells from chronic liver disease patients and healthy individuals. Methods Huh7 cells were transfected independently with ALR and miRNA‐26a expression vectors, and their effects on cell proliferation, the expression of miRNA‐26a, and activation of the phosphatase and tensin homolog and Akt signaling pathways were determined. The experiments were repeated on mesenchymal stem cells derived from healthy individuals and chronic liver disease patients to see whether the observations can be replicated in primary cells. Results Overexpression of ALR or miRNA‐26a resulted in an increase of the phosphorylation of Akt and cyclin D1 expression, whereas it resulted in decreased levels of p‐GSK‐3β and phosphatase and tensin homolog in Huh7 cells. The inhibition of ALR expression by ALR siRNA or anti‐miR‐26a decreased the Akt/cyclin D1 signaling pathway, leading to decreased proliferation. Mesenchymal stem cells isolated from the chronic liver disease patients had a higher ALR expression, while the mesenchymal stem cells isolated from healthy volunteers responded to the growth factor treatments for increased ALR expression. It was found that there was a significant increase in miRNA‐26a expression and proliferation. Conclusions These data clearly showed that ALR induced the expression of miRNA‐26a, which downregulated phosphatase and tensin homolog, resulting in an increased p‐Akt/cyclin D1 pathway and enhanced proliferation in hepatic cells.

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In this study, for the first time, we found that BANF1 inhibited HBV replication and restricted the viral load. However, as previously reported for other viruses, the results in this study showed that BAF1 phosphorylation/dephosphorylation is not involved in its antiviral activity against HBV.

Hepatitis B virus is a prototypical member of the hepadnavirus family and represent a leading cause of liver disease worldwide. Chronic HBV infection is one of the major ethology leading to cirrhosis and hepatocellular carcinoma (HCC). Upon infection, HBV interacts with various host proteins that play important role in successful infection establishment. Till date, various host proteins including SMC5/6, talin1, TRIM and tetherin have been established to possess anti-HBV activity. [1][2][3][4] Another host protein namely, DEAD box RNA helicase DDX3 has been shown to inhibit HBV, 5,6 however, the mechanism of inhibition remains unclear. HBV hijacks cellular pathways and subverts cellular machinery to benefit its own infection establishment. Autophagy is one such pathway that has been shown to be