Platelet-derived growth factor receptor beta (PDGFR-beta) (PDGFRB)

Platelet-derived growth factor receptor beta (PDGFRβ) is a cell-surface receptor tyrosine kinase (RTK) that plays a pivotal role in regulating mesenchymal cell proliferation, migration, and survival (UniProt: P09619). In the liver, PDGFRβ is minimally expressed in quiescent hepatic stellate cells (HSCs) but is dramatically upregulated upon their activation into myofibroblasts following chronic injury (Borkham-Kamphorst & Weiskirchen, 2016, Gene). Binding of its primary ligand, PDGF-BB, induces receptor dimerization and autophosphorylation, which activates downstream signaling pathways including Ras/MAPK, PI3K/Akt, and PLC-γ (Ying et al., 2017, Oncotarget). This signaling cascade is a primary driver of the fibrogenic response, leading to the excessive deposition of extracellular matrix components that characterize liver fibrosis and cirrhosis (Kocabayoglu et al., 2015, Journal of Hepatology). Consequently, PDGFRβ is a key therapeutic target for anti-fibrotic interventions, with several small-molecule kinase inhibitors like imatinib and nintedanib demonstrating the ability to attenuate HSC activation and fibrotic progression in preclinical models (Bansal et al., 2015, Journal of Controlled Release). However, the systemic use of these inhibitors is often limited by off-target effects, prompting research into myofibroblast-specific delivery systems to improve safety and efficacy (Frangogiannis, 2020, Nature Reviews Cardiology).

Other names

CD140 antigen-like family member BPlatelet-derived growth factor receptor 2PDGFR-betaCD140bPDGFR1JTK12Beta-type platelet-derived growth factor receptor

Inhibition of the intracellular tyrosine kinase domain by competing with ATP binding, thereby preventing autophosphorylation and downstream signaling through MAPK, PI3K/Akt, and PLC-gamma pathways (DrugBank: DB00619; PubMed: 22432445).