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

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

Shengbiao Li #  1 , Mi Li #  2 , Yi Zhang #  1 , Ji Chen  2 , Jiapan Li  1 , Shubo Fu  1 , Jingyan Yi  3 , Rong Li  4 , Gan Qiao  5 , Yang Yu  6 , Chunxiang Zhang  7 , Qiuhong Li  8
Affiliations
Review

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

Shengbiao Li et al. J Transl Med. .

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.

Keywords: Epithelial-Mesenchymal transition; Extracellular matrix; Organ fibrosis; Tetraspanins; Therapeutic perspectives.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: We give our consent for the manuscript to be published in Cell Communication and Signaling. Competing interests: The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Role of tetraspanins in liver fibrosis
Fig. 2
Fig. 2
Role of tetraspanins in cardiac fibrosis
Fig. 3
Fig. 3
Role of tetraspanins in pulmonary fibrosis
Fig. 4
Fig. 4
Role of Tetraspanins in Renal Fibrosis
Fig. 5
Fig. 5
Role of Tetraspanins in Dermal Fibrosis
Fig. 6
Fig. 6
Role of Tetraspanins in Corneal Fibrosis
Fig. 7
Fig. 7
Role of TSPANs across Organ Fibrosis
See this image and copyright information in PMC

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