Transforming growth factor beta-3 (TGFB3) (TGFB3)

Transforming growth factor beta-3 (TGF-β3) is a multifunctional cytokine belonging to the TGF-β superfamily, playing a critical role in embryogenesis, tissue development, and wound healing (UniProt, Wikipedia). Unlike other isoforms, TGF-β3 is specifically associated with scarless wound repair and the development of the secondary palate and lungs (MDPI Encyclopedia, PubMed). It signals through a heteromeric complex of type I and type II serine/threonine kinase receptors, primarily activating the canonical SMAD2/3 pathway to regulate gene expression (PMC). In disease, mutations in the TGFB3 gene are linked to Loeys-Dietz syndrome and arrhythmogenic right ventricular dysplasia, while dysregulated signaling contributes to various fibrotic conditions and cancer (MedlinePlus, PMC). In oncology, TGF-β3 exhibits a paradoxical role, acting as a tumor suppressor in early stages by inhibiting cell proliferation but promoting epithelial-mesenchymal transition and metastasis in advanced disease (PMC, PubMed). Therapeutic strategies include the use of recombinant TGF-β3 (e.g., avotermin) to reduce scarring and monoclonal antibodies (e.g., fresolimumab or isoform-specific agents) to inhibit its pro-fibrotic and pro-tumorigenic effects (PMC, MDPI). Recent drug development efforts have focused on isoform-specific inhibition to avoid the systemic toxicities, such as cardiovascular valve thickening, associated with pan-TGF-β blockade (PMC). Monitoring biomarkers like SMAD phosphorylation and specific matrix proteins can help assess the efficacy of these targeted interventions (PMC).

Other names

TGF-beta-3TGFB3ARVDARVD1LDS5RNHFTransforming growth factor, beta 3

Agonist of TGF-beta receptors (PubMed); Antagonist of TGF-beta ligands or receptors (PMC)