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  • Downregulation of miR‑141 deactivates hepatic stellate cells by targeting the PTEN/AKT/mTOR pathway.

Downregulation of miR‑141 deactivates hepatic stellate cells by targeting the PTEN/AKT/mTOR pathway.

International journal of molecular medicine (2020-04-23)
Haijun Liang, Xinwei Wang, Changyun Si, Yuxiu Duan, Baoxin Chen, Haixia Liang, Daokun Yang
ABSTRACT

The activation of hepatic stellate cells (HSCs) caused by stimulating factors or fibrogenic cytokines is the critical stage of liver fibrosis. Recent studies have demonstrated the influence of microRNAs (miRNAs or miRs) on HSC activation and transformation; however, the function and underlying mechanisms of miRNAs in HSC activation have not yet been completely clarified. In the present study, transforming growth factor β1 (TGF‑β1) was used to treat human HSC lines (HSC‑T6 and LX2 cells) to simulate the activation of HSCs in vivo and whether the expression of miRNAs in HSCs was affected by TGF‑β1 treatment was examined using a miRNA microarray. It was observed that miR‑141 was one of the most upregulated miRNAs during HSC activation. Functional analyses revealed that miR‑141 knockdown suppressed the viability of HSCs and inhibited the expression levels of pro‑fibrotic markers. In addition, phosphatase and tensin homolog (PTEN), a well‑known suppressor of the AKT/mammalian target of rapamycin (mTOR) pathway, was found to be directly targeted by miR‑141 in HSCs. More importantly, the knockdown of PTEN markedly reversed the suppressive effects of miR‑141 inhibition on the viability of and the expression levels of pro‑fibrotic markers during HSC activation. Finally, it was observed that the downregulation of miR‑141 blocked the TGF‑β1‑induced activation of the AKT/mTOR pathway in HSCs. On the whole, the findings of the present study indicate that miR‑141 inhibition suppresses HSC activation via the AKT/mTOR pathway by targeting PTEN, highlighting that miR‑141 may serve as a novel therapeutic target for liver fibrosis.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Transforming Growth Factor-β1 human, TGF-β1, recombinant, expressed in CHO cells, powder, suitable for cell culture
Sigma-Aldrich
(Tyr[SO3H]27)Cholecystokinin fragment 26-33 Amide, ≥97% (HPLC), powder