Transforming growth factor-beta signaling and collagen synthesis pathways (TGF-beta/Collagen pathway)

The Transforming growth factor-beta (TGF-beta) signaling and collagen synthesis pathways are fundamental biological processes that regulate cellular growth, differentiation, and the maintenance of the extracellular matrix (ECM) [4, 5]. TGF-beta ligands initiate signaling by binding to a complex of type I and type II serine/threonine kinase receptors, which subsequently phosphorylate Smad proteins [3, 4]. These Smads translocate to the nucleus to act as transcription factors, directly inducing the expression of various collagen genes and other ECM components [1, 3]. In pathological states such as chronic fibrosis and certain cancers, these pathways become hyperactivated, leading to excessive collagen deposition, tissue scarring, and tumor progression [3, 5]. Therapeutic interventions targeting these pathways include neutralizing antibodies, receptor kinase inhibitors, and antisense oligonucleotides, which aim to mitigate fibrotic remodeling and inhibit the pro-tumorigenic effects of TGF-beta [5]. However, the pleiotropic nature of TGF-beta signaling presents significant challenges, as systemic inhibition can lead to adverse effects such as impaired wound healing, cardiovascular issues, and the development of skin tumors [5].

Other names

TGF-beta signaling pathwayCollagen synthesis pathwayTGFB-Smad signalingTGF-beta/Smad2/3 pathway

Drugs targeting these pathways primarily act by neutralizing TGF-beta ligands (e.g., fresolimumab), inhibiting the kinase activity of TGF-beta type I receptors (e.g., galunisertib), or modulating downstream signaling and gene transcription to reduce collagen production (e.g., pirfenidone) [3, 5].