Roles of PDGF/PDGFR signaling in various organs

Abstract

Platelet-derived growth factors (PDGFs) ligands and their corresponding receptors, PDGF receptor (PDGFR)α and PDGFRβ, play a crucial role in controlling diverse biological functions, including cell growth, viability and migration. These growth factors bind to PDGFRs, which are receptor tyrosine kinases present on the surface of target cells. The interaction between PDGFs and PDGFRs induces receptor dimerization and subsequent activation through auto-phosphorylation, which in turn triggers a cascade of intracellular signaling pathways. PDGF/PDGFR signaling is essential for maintaining normal physiological functions, including tissue regeneration and growth. However, dysregulation of this signaling pathway leads to pathological conditions, including fibrosis, atherosclerosis, and cancer development in various organs. The pathological impact of PDGF/PDGFR signaling primarily stems from its capacity to promote excessive cell proliferation, enhanced migration, and increased extracellular matrix deposition, resulting in tissue overgrowth, scarring, and abnormal vessel formation. These processes are integral to the pathogenesis of fibrotic, neoplastic, and vascular disorders. Therefore, understanding these pathways is crucial for developing targeted treatments designed to inhibit PDGF/PDGFR signaling in these diseases. This review delves into the dual role of PDGF/PDGFR signaling in both physiological and pathophysiological contexts across different organs and provides insights into current pharmacological therapies designed to target the PDGF signaling pathway.

Keywords: Cancer; Fibrosis; Growth factor; Platelet-derived growth factor.

Fig. 1. Expression of various K

₊ channel subtypes in the small intestine, including the smooth muscle of the jejunum and mucosa/smooth muscle of the colon. Table (A) shows the subtypes with the highest expression levels. The bar graph (B) illustrates the differential expression across these tissues. The unit the expression is Fragments Per Kilobase of transcript per Million mapped reads (FPKM). PDGFRα, platelet-derived growth factor receptor α.

Fig. 2. The expression pattern of platelet-derived growth factor receptor

α (PDGFRα) was analyzed in various organs of 8-week-old Pdgfratm11(EGFP)Sor/J mice. Immunofluorescence imaging revealed PDGFRα expression (green) in the brain, lung, liver, ileum, and testis.