Mannose receptor modulates hepatic stellate cell activation and alleviates liver fibrosis through immune-fibrotic crosstalk.

BACKGROUND

Liver fibrosis is characterized by excessive extracellular matrix (ECM) deposition and hepatocellular dysfunction. Activation of hepatic stellate cells (HSCs) is central to this process, yet the underlying regulatory mechanisms remain incompletely understood. The mannose receptor (MR), a pattern-recognition receptor involved in immune modulation and tissue remodeling, has been implicated in fibrotic diseases, but its role in hepatic fibrosis remains unclear.

METHODS

A chronic liver fibrosis model was established in mice using repeated carbon tetrachloride (CCl4) injection. Histology, serum biochemistry, quantitative PCR, and Western blotting were used to evaluate fibrosis, HSC activation, and MR expression. Correlations between MR and inflammatory cytokines were analyzed. In vitro, MR overexpression was used to assess its role in transforming growth factor-β (TGF-β)-induced HSC activation.

RESULTS

CCl4-induced fibrosis resulted in hepatocyte injury, ECM accumulation, and elevated ALT, AST, and triglyceride levels. HSC activation, indicated by increased α-SMA and collagen I expression, accompanied fibrosis progression. MR expression in liver tissue and soluble MR (sMR) levels in serum were significantly increased and were associated with inflammatory cytokines. In vitro, MR overexpression suppressed TGF-β-induced HSC activation without altering total Smad-3 expression.

CONCLUSION

These findings suggest that MR may play a regulatory role in hepatic fibrogenesis by modulating HSC activation and ECM deposition, potentially through interactions with the inflammatory microenvironment. Elevated MR and sMR levels may serve as candidate biomarkers for fibrosis progression.