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Published on: April 16, 2019
[Hepatic fibrosis aggravation in nuclear autoantigenic sperm protein (NASP) mutant mice induced by concanavalin A]
Yanyan Zhang1, Hongwei Yan2, Jun Zhu1
1Department of Immunology, Weifang Medical University, Weifang 261053, China.
Abstract:
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.
Insights
Nuclear autoantigenic sperm protein (NASP) gene mutation worsens liver fibrosis in mice by increasing tumor necrosis factor-alpha (TNF-α) and altering T lymphocyte subsets, promoting hepatic stellate cell activation.
Area of Science:
- Immunology
- Hepatology
- Molecular Biology
Background:
- Liver fibrosis is a significant health concern.
- Nuclear autoantigenic sperm protein (NASP) role in liver fibrosis is not well understood.
Purpose of the Study:
- To investigate the effect of nuclear autoantigenic sperm protein (NASP) gene mutation on concanavalin A (ConA)-induced liver fibrosis in mice.
- To elucidate the underlying mechanisms of NASP gene mutation in liver fibrosis.
Main Methods:
- Established a mouse model of liver fibrosis using ConA injection.
- Assessed histopathological changes, collagen deposition, and alpha-smooth muscle actin (α-SMA) expression.
- Measured serum liver enzymes (ALT, AST), inflammatory cytokines (TNF-α, IFN-γ), and hepatic gene expression (Col1, Col3).
- Analyzed T lymphocyte subsets in liver tissue using flow cytometry.
Main Results:
- NASP mutant mice showed aggravated liver fibrosis with increased collagen deposition and α-SMA expression compared to wild-type mice.
- Significantly elevated serum ALT and TNF-α levels were observed in NASP mutant mice.
- A marked decrease in CD4+CD44hi T lymphocyte subsets within the liver tissue of NASP mutant mice.
Conclusions:
- Mutation of the NASP gene exacerbates liver fibrosis in mice.
- This exacerbation is mediated by increased TNF-α release, altered liver T lymphocyte populations, and enhanced hepatic stellate cell activation.
