Hepatic fibrosis aggravation in nuclear autoantigenic sperm protein (NASP) mutant mice induced by concanavalin A].

Objective To investigate how mutation of nuclear autoantigenic sperm protein (NASP) gene affects mouse liver fibrosis induced by concanavalinA (ConA) and its mechanism. Methods The wild-type B6 (B6-WT) mice were used as a control group, and the NASP mutant B6 (B6-NASPM) mice as an experimental group. The mice were injected with ConA via tail vein once a week for 8 weeks to establish the model of liver fibrosis. The histopathological changes were observed by HE staining, the collagen fiber deposition by Masson staining, smooth muscle alpha-actin (α-SMA) expression in liver tissue by immunohistochemical staining. The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by microplate assay. The serum tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) were measured by ELISA. The mRNA expressions of type I collagen (Col1) and Col3 in liver tissue were determined by real-time quantitative PCR, and the changes of T lymphocyte subsets in liver tissue were detected by flow cytometry. Results Compared with the B6-WT group, B6-NASPM group had disordered liver structure and no significant changes in mRNA expression of Col 1 and Col3, but the collagen fiber hyperplasia and α-SMA expression in liver tissue were more obvious, and the levels of serum ALT and TNF-α were significantly increased. In addition, the proportion and number of CD4+CD44hi T lymphocyte subsets in liver tissue were markedly decreased. Conclusion Mutation of NASP gene aggravates mouse liver fibrosis by increasing the release of TNF-α, changing the proportion of T lymphocyte subsets in liver tissue and promoting the activation of hepatic stellate cells.

Citation

Yanyan Zhang, Hongwei Yan, Jun Zhu, Long Chen, Hui Wang, Jiyu Ju. Hepatic fibrosis aggravation in nuclear autoantigenic sperm protein (NASP) mutant mice induced by concanavalin A]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology. 2022 Jul;38(7):577-583

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PMID: 35786450

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