TGF‑β1‑induced autophagy activates hepatic stellate cells via the ERK and JNK signaling pathways

Zhang,Jing; Jiang,Na; Ping,Jian; Xu,Lieming

doi:10.3892/ijmm.2020.4778

TGF‑β1‑induced autophagy activates hepatic stellate cells via the ERK and JNK signaling pathways

Authors:
- Jing Zhang
- Na Jiang
- Jian Ping
- Lieming Xu
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Affiliations: Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
Published online on: November 3, 2020 https://doi.org/10.3892/ijmm.2020.4778
Pages: 256-266
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Transforming growth factor β1 (TGF‑β1) is one of the most important fibrogenic factors promoting the activation of hepatic stellate cells (HSCs). Autophagy is a process used by cells to degrade and recycle cellular proteins. Although TGF‑β1 induces autophagy in several other cellular systems, the association between its effect on fibrogenesis and autophagy in HSCs have not been determined. Liver tissues from C57BL/6 mice and the mouse HSC line JS1 were analyzed. Acute and chronic liver injury models were induced by carbon tetrachloride (CCl4), and JS1 cells were stimulated by TGF‑β1 to assess the mechanism and relationship between autophagy and fibrosis. Liver tissues from acute and chronic injury models induced by CCl4 demonstrated evidence of increased autophagic activity, as assessed by the expression of the microtubule‑associated protein 1 light chain 3BII protein. TGF‑β1 stimulated the activation of JS1 cells and simultaneously increased autophagy flux. However, this effect was attenuated when autophagy was inhibited using chloroquine, 3‑methyladenine or lentiviral short hairpin RNA‑mediated knockdown of autophagy‑related gene 7. Furthermore, whether MAPK, including ERK, JNK and p38 MAPK cascades were associated with TGF‑β1‑induced autophagy in JS1 cells was determined. Subsequently, it was shown that the ERK inhibitor, PD98059, and JNK inhibitor, SP600125, were able to reverse TGF‑β1‑induced autophagy and fibrosis. The results of the present study suggest that TGF‑β1‑induced autophagy is involved in the activation of JS1 cells, possibly through activation of the ERK and JNK signaling pathways.

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