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SVIP alleviates CCl4-induced liver fibrosis via activating autophagy and protecting hepatocytes.

ABSTRACT: Prolonged parenchymal cell death leads to activation of fibrogenic cells and extracellular matrix accumulation and eventually liver fibrosis. Autophagy, a major catabolic process of intracellular degradation and recycling, participates in hepatic fibrosis. However, the precise role of autophagy in the pathogenesis of hepatic fibrosis is controversial. The present study aims to investigate the key role of small VCP/p97 interacting protein (SVIP) against CCl4-induced hepatic fibrosis via activating autophagy. Autophagy could be activated by SVIP in HepG2 cells, but starvation cannot increase SVIP expression in vitro and in vivo. Moreover, SVIP expression, in agreement with autophagic activity and the volume of lipid droplets, first increases and then decreases during the progression of liver fibrosis with CCl4 treatment in vivo and in vivo. Further, overexpression of SVIP can protect HepG2 cells from the toxicity of CCl4, which could be enhanced by starvation. Finally, starvation keeps SVIP and autophagy at such high levels in the rat livers that markedly delays the progress of hepatic fibrosis. Probably, the protective effect of SVIP is associated with stabilizing nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) and transcription factor EB (TFEB). The current study provides insight into the biological role of SVIP and autophagy in regulating hepatic fibrosis, targeting SVIP might be a novel therapeutic strategy in the future.

SUBMITTER: Jia D

PROVIDER: S-EPMC6347612 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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SVIP alleviates CCl<sub>4</sub>-induced liver fibrosis via activating autophagy and protecting hepatocytes.

Jia Dan D Wang Yuan Yuan YY Wang Pin P Huang Yao Y Liang David Yuke DY Wang Dongmei D Cheng Chuandong C Zhang Caihua C Guo Lianying L Liang Pin P Wang Yang Y Jia Yujie Y Li Cong C

Cell death & disease 20190125 2

Prolonged parenchymal cell death leads to activation of fibrogenic cells and extracellular matrix accumulation and eventually liver fibrosis. Autophagy, a major catabolic process of intracellular degradation and recycling, participates in hepatic fibrosis. However, the precise role of autophagy in the pathogenesis of hepatic fibrosis is controversial. The present study aims to investigate the key role of small VCP/p97 interacting protein (SVIP) against CCl<sub>4</sub>-induced hepatic fibrosis vi ...[more]

PMID: 30683843

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Dataset Information

SVIP alleviates CCl4-induced liver fibrosis via activating autophagy and protecting hepatocytes.

Publications

SVIP alleviates CCl<sub>4</sub>-induced liver fibrosis via activating autophagy and protecting hepatocytes.

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