TGFB3

TGFB3 encodes Transforming Growth Factor Beta 3, a secreted cytokine belonging to the TGF-β superfamily. Also known as TGF-β3, it regulates diverse cellular processes including proliferation, differentiation, apoptosis, and extracellular matrix (ECM) synthesis. Mechanistically, TGFB3 binds to transmembrane serine/threonine kinase receptors (TβRII/TβRI), initiating SMAD-dependent signaling via SMAD2/3 phosphorylation and subsequent nuclear translocation with SMAD4. Non-canonical pathways, such as MAPK and PI3K/Akt, are also modulated. This pleiotropic protein is critical in embryogenesis, wound healing, and immune regulation, with tightly controlled spatiotemporal expression.
Aberrant TGFB3 expression correlates with pathological fibrosis, cancer progression, and cardiovascular disorders. Notably, dysregulated TGFB3 signaling has been implicated in syndromic disorders such as Marfan syndrome through interactions with fibrillin-1. In oncology, TGFB3 exhibits dual roles, suppressing early tumorigenesis while promoting metastasis via epithelial-mesenchymal transition (EMT). Therapeutic targeting focuses on pan-TGF-β inhibitors like fresolimumab (monoclonal antibody) and galunisertib (TβRI kinase inhibitor), though isoform-specific modulation remains challenging. Recent advances in antisense oligonucleotides and gene-editing approaches aim to address TGFB3's context-dependent pathologies while minimizing systemic toxicity associated with broad pathway inhibition.