Kinase targets in activated myofibroblasts

Kinase targets in activated myofibroblasts represent a diverse group of signaling proteins that drive the transition of quiescent fibroblasts into contractile, matrix-producing myofibroblasts, a process central to pathological fibrosis [2, 7]. This group includes receptor tyrosine kinases (RTKs) such as Platelet-Derived Growth Factor Receptor (PDGFR) and Fibroblast Growth Factor Receptor (FGFR), which promote cellular proliferation and migration [6, 12]. Transforming Growth Factor-beta (TGF-beta) receptor kinases, particularly TGF-beta receptor type 1 (ALK5), are critical mediators that activate both canonical Smad pathways and non-canonical pathways involving Mitogen-Activated Protein Kinases (MAPKs) and PI3K/Akt/mTOR [5, 9, 10]. Non-receptor tyrosine kinases, including Src family kinases and Focal Adhesion Kinase (FAK), integrate signals from the extracellular matrix to regulate cytoskeletal organization and alpha-smooth muscle actin (alpha-SMA) expression [1, 3, 4]. Additionally, Rho-associated protein kinase (ROCK) modulates myofibroblast contraction and stress fiber formation [5, 12]. Therapeutic targeting of these kinases, exemplified by the multi-kinase inhibitor nintedanib, aims to disrupt these essential activation signals to treat fibrotic diseases like idiopathic pulmonary fibrosis [8, 12]. However, the broad physiological roles of these kinases often lead to significant safety concerns and therapeutic challenges [12].

Other names

Myofibroblast activation kinasesFibrogenic signaling kinasesKinases in fibroblast-to-myofibroblast transitionFMT-associated kinases

Inhibition of various receptor and non-receptor kinases (e.g., PDGFR, FGFR, VEGFR, Src, FAK, TGFBR1, ROCK, MAPK) to disrupt fibrogenic signaling and myofibroblast activation.