Myofibroblast proliferation

Myofibroblast proliferation refers to the expansion of a specialized population of contractile mesenchymal cells that are primary drivers of tissue repair and pathological fibrosis [1, 14, 15]. These cells are characterized by the neo-expression of alpha-smooth muscle actin (alpha-SMA) and are responsible for the excessive deposition of extracellular matrix (ECM) components like collagen and fibronectin [14, 15]. Under normal conditions, myofibroblasts proliferate to heal wounds and then undergo apoptosis; however, in chronic diseases, their persistent proliferation leads to organ stiffness and functional failure [7, 14]. This process is largely driven by growth factors such as transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF), which activate various intracellular signaling cascades including the SMAD, MAPK, and PI3K pathways [1, 2, 5]. Because myofibroblasts are the central effectors of fibrotic remodeling, inhibiting their proliferation is a major therapeutic goal in treating conditions like idiopathic pulmonary fibrosis, renal fibrosis, and liver cirrhosis [1, 5, 9]. Current pharmacological agents like nintedanib and pirfenidone work by blocking the tyrosine kinases and cytokines that stimulate this proliferative response [1, 14].

Other names

Myofibroblast expansionActivated fibroblast proliferationFibroblast-to-myofibroblast proliferation

Drugs inhibit myofibroblast proliferation by blocking upstream signaling pathways such as TGF-beta receptors, receptor tyrosine kinases (PDGFR, VEGFR, FGFR), or downstream effectors like Rho-associated protein kinase (ROCK) and various MAP kinases [1, 4, 7].