Category: signaling
Transforming growth factor β family ligands → type II + type I serine/threonine kinase receptors → R-SMAD (SMAD2/3) phosphorylation → R-SMAD + co-SMAD (SMAD4) complex → nuclear translocation → transcription of ECM genes (collagen, fibronectin, integrins) + EMT genes. Master driver of FIBROSIS in IPF, hepatic, renal, scleroderma, post-surgical scarring. Pharmacology: pirfenidone (multimodal antifibrotic, partly anti-TGF-β; approved for IPF + slows FVC decline); nintedanib (multi-kinase inhibitor PDGFR + FGFR + VEGFR; reduces IPF FVC decline). Direct TGF-β neutralization (fresolimumab, etc.) trialed in fibrosis + oncology with mixed results. Bone morphogenetic proteins (BMPs) are TGF-β family but signal through SMAD1/5/8.