The Function of the TGFβ Signaling Pathway in Connective Tissue Diseases: From Biology to Clinical Application

Simin Yuan,1 Wen Zhu,2 Yue Wang,1,2 Lili Yu1,3,4 1Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, People’s Republic of China; 2Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3State Key Laboratory of Mechanism and Quality of Chinese Medicine, Macau University of Science and Technology, Macau, People’s Republic of China; 4Macau University of Science and Technology Zhuhai MUST Science and Technology Research Institute, Zhuhai, Guangdong, People’s Republic of ChinaCorrespondence: Yue Wang; Lili Yu, Email [email protected]; [email protected]: Connective tissue diseases (CTDs) are characterized by a diverse array of symptoms, including persistent inflammation, immune system dysfunction, and fibrosis. The transforming growth factor-β (TGFβ) signaling pathway is crucial in fibrosis, dysregulated immune responses, and vascular injury associated with CTDs. TGFβ signaling facilitates the pathological progression of CTDs by modulating fibroblast activation, extracellular matrix accumulation, and immune cell activity. Based on a systematic search of PubMed and Web of Science, this narrative review reveals the dual role of TGFβ signaling in CTD pathogenesis and its therapeutic challenges. This review examines the mechanistic role of the TGFβ signaling pathway in various CTDs, such as systemic sclerosis (SSc), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren’s syndrome (SS). The review further examines the interplay between classical and non-classical pathways of the TGFβ signaling system and its implications in fibrosis and immunomodulation. The clinical applications of TGFβ as a potential therapeutic target are also discussed, with a special focus on treatment of ameliorating CTDs-associated fibrosis and immune abnormalities. These findings underscore the pivotal role of TGFβ signaling in fibrosis and immune regulation, highlighting opportunities for more precise and individualized therapeutic strategies.Keywords: TGF-β signaling pathway, connective tissue disorders, fibrosis, immunomodulation, therapeutic targets