MIF/CD74 axis in hepatic stellate cells mediates HBV-related liver fibrosis.

Chronic hepatitis B virus (HBV) infection is a major risk factor for liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Despite advances in understanding HBV-related liver diseases, effective therapeutic strategies remain limited. Macrophage migration inhibitory factor (MIF) has been implicated in various inflammatory and fibrotic conditions, but its role in HBV-induced liver fibrosis has not been fully explored. This study investigates the involvement of MIF in liver fibrosis and evaluates its potential as a therapeutic target. We found that MIF expression was significantly elevated in hepatic stellate cells (HSCs) following stimulation with HBVcc (HBV cell culture) or HBV surface antigen (HBsAg). Through its receptor CD74, MIF enhanced the TGF-β/SMAD signaling pathway, promoting HSC activation and liver fibrosis progression. Histological analysis revealed higher MIF and CD74 expression in HBsAg-positive individuals compared to HBsAg-negative controls. Moreover, MIF expression correlated with the activation of fibrosis markers, including α-SMA and TGF-β-related proteins. Inhibition of MIF with the specific inhibitor ISO-1 attenuated fibrosis progression, suggesting that targeting MIF could offer a promising approach for treating HBV-related liver fibrosis. Our findings underscore the critical role of the MIF/CD74 axis in liver fibrosis and provide a basis for future therapeutic strategies targeting MIF in chronic liver diseases.