miR221 regulates TGF-β1-induced HSC activation through inhibiting autophagy by directly targeting LAMP2

Cheng,Ran; Xu,Hao; Hong,Yang

doi:10.3892/mmr.2021.12417

miR221 regulates TGF-β1-induced HSC activation through inhibiting autophagy by directly targeting LAMP2

Authors:
- Ran Cheng
- Hao Xu
- Yang Hong
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Affiliations: The First Department of Hepatobiliary Surgery, Tangshan Gongren Hospital, Tangshan, Hebei 063000, P.R. China, Medical Insurance Office, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China, Department of Clinical Pharmacology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China
Published online on: September 7, 2021 https://doi.org/10.3892/mmr.2021.12417
Article Number: 777
Copyright: © Cheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Liver fibrosis is a serious threat to human life and health. Activated hepatic stellate cells (HSCs) play a key role in the occurrence and development of liver fibrosis. Studies have reported that microRNAs (miRNAs/miRs) are involved in the pathological process of fibrosis, as well as its relevance in clinical diagnosis. However, the role of miR221 in hepatic fibrosis remains controversial. Remarkably, transforming growth factor‑β (TGF‑β1) caused HSC dysfunction in autophagic activation, characterized by an increase in P62 aggregation and LC3II expression. The present study aimed to determine whether autophagy regulates hepatic fibrosis by mediating HSC activation and explore the potential targets leading to the sequence of events associated with miR221. The expression of miR221 was quantified in a liver fibrosis model in vivo and in vitro, and its specific target gene lysosome‑associated membrane glycoprotein 2 (LAMP2) was predicted by bioinformatics. The results showed that the expression levels of collagen‑I (COL‑I) and α‑smooth muscle actin (α‑SMA) were increased in miR221‑overexpressing LX2 cells, while the autophagy inducer rapamycin reversed the inhibition of autophagic flux induced by miR221. Additionally, the overexpression of LAMP2 could significantly inhibit TGF‑β1‑induced COL‑I and α‑SMA expression, which was similar to the effect of the miR221 inhibitor on the regulation of TGF‑β1‑induced HSC activation. These results indicated that miR221 may regulate TGF‑β1‑induced HSC activation through inhibiting autolysosome function by directly targeting LAMP2. The molecular mechanism of miR221 in regulating TGF‑β1‑induced HSC activation may provide novel insight into therapies to ameliorate the pathological progression of liver fibrosis.

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