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Platelet-derived growth factor subunit A (PDGF-AA) is a homodimeric glycoprotein belonging to the platelet-derived growth factor family, consisting of two disulfide-linked A-chains [6, 9, 14]. It acts as a potent mitogen and chemoattractant for cells of mesenchymal origin, including fibroblasts, smooth muscle cells, and glial cells [6, 8, 13]. Biologically, PDGF-AA is essential for normal embryonic development, wound healing, and angiogenesis, primarily signaling through the Platelet-derived growth factor receptor alpha (PDGFR-alpha) [5, 8, 13, 40]. Pathologically, dysregulation of PDGF-AA is linked to the progression of various cancers, such as glioblastoma and hepatocellular carcinoma, where it often drives autocrine or paracrine growth loops [3, 12, 17, 33]. It also plays a significant role in fibrotic diseases and atherosclerosis by promoting excessive fibroblast activation and extracellular matrix deposition [1, 13, 17, 29]. Therapeutic strategies targeting the PDGF-AA axis include monoclonal antibodies like olaratumab, which blocks the receptor, and small-molecule tyrosine kinase inhibitors like imatinib that disrupt downstream signaling [1, 22, 23, 32].
Inhibition of receptor tyrosine kinase (RTK) activity [1, 24, 32], neutralization of ligand binding to the receptor [5, 22, 23], and sequestration of the growth factor ligand [20, 39].
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