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

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.