Transforming growth factor beta 1 (TGF-beta 1) (TGFB1)

Transforming growth factor beta 1 (TGF-beta 1) is a multifunctional cytokine that serves as the master regulator of the fibrotic response in the heart. It acts by binding to a heterodimeric receptor complex (TGFBR1 and TGFBR2), triggering canonical Smad-dependent and non-canonical signaling pathways that drive the differentiation of cardiac fibroblasts into activated myofibroblasts. These myofibroblasts are responsible for the excessive synthesis and deposition of extracellular matrix (ECM) proteins, primarily Type I (COL1A1, COL1A2) and Type III (COL3A1) collagens. In the context of myocardial injury or chronic stress, persistent activation of this pathway leads to myocardial fibrosis, which increases ventricular stiffness and contributes to the progression of heart failure. Therapeutic strategies targeting this pathway include neutralizing antibodies, receptor kinase inhibitors, and indirect modulators like pirfenidone and angiotensin receptor blockers, aimed at reducing scar formation and preserving cardiac function.

Other names

Transforming growth factor beta-1TGFB1TGF-beta 1Prepro-TGF-beta-1Latency-associated peptide (LAP)TGF-beta-1-induced myocardial fibrosis pathway

Inhibition of TGF-beta 1 ligand-receptor binding, inhibition of TGF-beta receptor type 1 (ALK5) kinase activity, and reduction of TGF-beta 1 synthesis or activation.