PTP1B restrains the apoptosis of activated hepatic stellate cells (HSCs) induced by TRAIL during the resolution of liver fibrosis

doi:10.5246/jcps.2023.11.070

Abstract

Abstract:

The activation of hepatic stellate cells (HSCs) is a key event in hepatic fibrosis (HF). As a reversible progress, HF can be reversed by inactivation and apoptosis of activated HSCs (aHSCs). We previously found that protein tyrosine phosphatase 1B (PTP1B) promotes HSC activation and inhibits aHSCs inactivation during the progressive and recovery stages of HF. Nevertheless, the effect of PTP1B on apoptosis of aHSCs remains unknown. Therefore, we investigated the link between PTP1B and aHSCs apoptosis. Mouse liver fibrosis and reversal models were established for this purpose. After activated by transforming growth factor-β1 (TGF-β1), HSC-T6 cells were treated with TNF-related apoptosis-inducing ligand (TRAIL) to mimic apoptosis of aHSCs in vitro. The results showed that PTP1B was elevated in the fibrotic liver, but reduced after recovery. Consistently, PTP1B was highly-expressed in aHSCs, but declined in apoptotic aHSCs. Furthermore, PTP1B inhibited the alleviating effect of TRAIL in HF, indicating that TRAIL did not decrease collagen and α-smooth muscle actin (α-SMA) levels after PTP1B overexpression. Moreover, overexpression of PTP1B significantly restrained the pro-apoptotic effect of TRAIL, decreasing the number of apoptotic cells and apoptosis-related proteins. These observations revealed that PTP1B is involved in the reversal of HF by influencing the apoptosis of aHSCs.

Key words: Protein tyrosine phosphatase 1B, Liver fibrosis, Hepatic stellate cells, TNF-related apoptosis-inducing ligand, Apoptosis

Supporting:

Peijie Chen, Yuntian Zhang. PTP1B restrains the apoptosis of activated hepatic stellate cells (HSCs) induced by TRAIL during the resolution of liver fibrosis[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(11): 867-880.

Figures/Tables 5

References 47

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