四跨膜蛋白在器官纤维化中的作用：机制与治疗前景

The role of tetraspanins in organ fibrosis: mechanisms and therapeutic perspectives.

作者信息

Li Shengbiao, Li Mi, Zhang Yi, Chen Ji, Li Jiapan, Fu Shubo, Yi Jingyan, Li Rong, Qiao Gan, Yu Yang, Zhang Chunxiang, Li Qiuhong

机构信息

Department of Medical Cell Biology and Genetics, School of Basic Medical Sciences, Key Laboratory of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, 646000, Sichuan, China.

Department of Histology and Embryology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, 646000, Sichuan, China.

出版信息

J Transl Med. 2025 Sep 24;23(1):1007. doi: 10.1186/s12967-025-06890-9.

DOI:10.1186/s12967-025-06890-9

PMID:40993816

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12462079/

Abstract

Fibrosis, caused by excessive extracellular matrix (ECM) deposition, is a major contributor to organ dysfunction and mortality. Tetraspanins (TSPANs) have emerged as key regulators of fibrotic processes across various organs. This review examines the roles of TSPANs (e.g., TM4SF5, CD151, CD63, and CD9) in fibrosis in the liver, heart, lungs, kidneys, skin, and cornea, focusing on their influence on fibroblast activation, epithelial-mesenchymal transition (EMT), inflammation, and ECM remodeling through TGF-β/Smad, STAT3, and integrin signaling. Potential TSPAN-targeted therapies, such as monoclonal antibodies, RNA silencing, and exosome engineering are also evaluated. Despite promising preclinical results, challenges remain in tissue specificity, delivery, and clinical application for TSPAN-based antifibrotic therapies.

摘要

由细胞外基质（ECM）过度沉积引起的纤维化是导致器官功能障碍和死亡的主要因素。四跨膜蛋白（TSPANs）已成为多种器官纤维化过程的关键调节因子。本综述探讨了TSPANs（如TM4SF5、CD151、CD63和CD9）在肝脏、心脏、肺、肾脏、皮肤和角膜纤维化中的作用，重点关注它们通过TGF-β/Smad、STAT3和整合素信号通路对成纤维细胞激活、上皮-间质转化（EMT）、炎症和ECM重塑的影响。还评估了潜在的以TSPAN为靶点的治疗方法，如单克隆抗体、RNA沉默和外泌体工程。尽管临床前结果很有前景，但基于TSPAN的抗纤维化疗法在组织特异性、递送和临床应用方面仍面临挑战。