Cheng Jun-Ya, Shan Guan-Yue, Wan Hui, Zhang Yu-Xin, Gao Zhi-Cheng, Shi Yun-Peng, Liu Fei, Yan Wei-Qun, Li Hai-Jun
Department of Bioengineering, Jilin University School of Pharmaceutical Sciences, Changchun, Jilin Province 130021, China; Department of Transplantation Immunology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin Province 130061, China.
Department of Transplantation Immunology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin Province 130061, China.
Int Immunopharmacol. 2025 Feb 6;147:113929. doi: 10.1016/j.intimp.2024.113929. Epub 2025 Jan 2.
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.
慢性乙型肝炎病毒（HBV）感染是肝纤维化、肝硬化和肝细胞癌（HCC）的主要危险因素。尽管在理解HBV相关肝病方面取得了进展，但有效的治疗策略仍然有限。巨噬细胞迁移抑制因子（MIF）已被证明与多种炎症和纤维化疾病有关，但其在HBV诱导的肝纤维化中的作用尚未得到充分研究。本研究调查了MIF在肝纤维化中的作用，并评估了其作为治疗靶点的潜力。我们发现，用HBVcc（HBV细胞培养物）或乙肝表面抗原（HBsAg）刺激后，肝星状细胞（HSCs）中MIF的表达显著升高。通过其受体CD74，MIF增强了TGF-β/SMAD信号通路，促进了肝星状细胞的激活和肝纤维化的进展。组织学分析显示，与HBsAg阴性对照相比，HBsAg阳性个体中MIF和CD74的表达更高。此外，MIF的表达与纤维化标志物的激活相关，包括α-SMA和TGF-β相关蛋白。用特异性抑制剂ISO-1抑制MIF可减轻纤维化进展，这表明靶向MIF可能为治疗HBV相关肝纤维化提供一种有前景的方法。我们的研究结果强调了MIF/CD74轴在肝纤维化中的关键作用，并为未来针对慢性肝病中MIF的治疗策略提供了基础。
