Relationship between SHP2 expression and the activation and proliferation of hepatic stellate cells in liver tissues of rats with CCl4-induced liver fibrosis

Abstract

Abstract: Objective To explore the relationship between SH2 domain-containing protein tyrosine phosphatase 2 (SHP2)expression and the activation and proliferation of hepatic stellate cells (HSC)in liver tissues.Methods A liver fibrosis rat model was established by using CCl₄ treatment. 50 healthy male SD rats were randomly divided into control group (10)and model group (40). Masson's trichrome staining and Hematoxylin and eosin (HE)staining were used to detect histological changes in liver tissues of rats. The expressions of SHP2 and alpha-smooth muscle action (α-SMA)in hepatic tissues of rats were analyzed through immunohistochemical staining. The expressions of SHP2 in HSC in vivo were analyzed through α-SMA and SHP2 immunofluorescence double-labeling.Results Compared with the integrated optical density (IOD)of α-SMA in the liver tissues of the control group (0.09±0.01), the IOD of α-SMA in the fibrotic liver tissues of rats at weekly time points (2, 4, 6, 8 weeks)during making model (0.13±0.01, 0.18±0.01, 0.24±0.02, 0.28±0.02)notably increased (P<0.05), and the more severe liver fibrosis, the higher α-SMA expression of hepatic tissues in rats (P<0.05). Since the α-SMA is a marker of activated HSC, the activation and proliferation of HSC in vivo gradually accelerated with the progress of liver fibrosis. Compared with the IOD of SHP2 in the liver tissues of the control group (0.19±0.01), the IOD of SHP2 in the fibrotic liver tissues of rats in the model group (0.23±0.01, 0.27±0.01, 0.30±0.01, 0.33±0.01)significantly increased (P<0.05), and the more severe liver fibrosis, the higher SHP2 expression in hepatic tissues of rats (P<0.05). The α-SMA and SHP2 immunofluorescence double-labeling showed that, at weekly time points (2, 4, 6, 8 weeks)during model formation, the percentage of activated HSC expressing SHP2 to the all activated HSC (54%±3%, 62%±2%, 73%±4%, 86%±3%)gradually heightened (P<0.05).Conclusion In rats with CCl₄-induced liver fibrosis, the expressions of SHP2 in both liver tissues and HSC in vivo have an evident positive correlation with the activation and proliferation of HSC.

Key words: Liver fibrosis, Hepatic stellate cells, SHP2, Proliferation

ZHANG Peng-lei, ZHANG Ming-ting, HAO Li-sen, JIN Li-min, PAN En-liang, HE Yu, MIAO Xiao-jia, WANG Wei. Relationship between SHP2 expression and the activation and proliferation of hepatic stellate cells in liver tissues of rats with CCl₄-induced liver fibrosis[J]. Chinese Hepatolgy, 2023, 28(5): 549-553.

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Relationship between SHP2 expression and the activation and proliferation of hepatic stellate cells in liver tissues of rats with CCl₄-induced liver fibrosis

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