Platelet-derived growth factor (PDGF) was discovered as a serum-derived component necessary for the growth of smooth muscle cells, fibroblasts, and glial cells. Although PDGF signaling is most closely associated with mesenchymal cells, PDGFs and PDGF receptors are widely expressed in the mammalian central nervous system[2]. Today the PDGF family of growth factors consists of five different disulphide-linked dimers built up of four different polypeptide chains encoded by four different genes. These isoforms, PDGF-AA, PDGF-AB, PDGF-BB, PDGF-CC and PDGF-DD, act via two receptor tyrosine kinases, PDGF receptors alpha and beta[3]. PDGFRα expression decreases with adipocyte lineage, while PDGFRβ inhibits white adipocyte differentiation. In addition, PDGFRβ induces proliferation, migration, and angiogenesis and up-regulates the expression of paracrine factors in adipose-derived stem cells(ASCs)[4].Overactivity of PDGF receptor signaling, by overexpression or mutational events, may drive tumor cell growth. In addition, pericytes of the vasculature and fibroblasts and myofibroblasts of the stroma of solid tumors express PDGF receptors, and PDGF stimulation of such cells promotes tumorigenesis[5]. Seralutinib(GB002) is an inhibitor of inhaled PDGFRα and PDGFRβ. It is used in the study for pulmonary arterial hypertension.GB002 dose-and time-dependently induces lung BMPR2 protein expression.GB002-mediated inhibition of lung PDGFRα/β phosphorylation in healthy Sprague Dawley rats immediately post inhalation[6].
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