PDGF: a multifunctional growth factor

Abstract

hPDGF is the major growth factor of human blood serum. In vivo, it is apparently synthesized by megakaryocytes and is transported in blood stored in the alpha granules of platelets. hPDGF is a heterodimer of two homologous polypeptide chains (PDGF-1(A) and PDGF-2(B] linked together by disulphide bonds. The PDGF-1(A) chain is encoded by a gene localized in chromosome 7 and the PDGF-2(B) chain is encoded by the c-sis proto-oncogene localized in chromosome 22. The hPDGF heterodimer and its two isoforms, the PDGF-1(A) and PDGF-2(B) homodimers, are potent mitogens and chemoattractants for target cells such as diploid fibroblasts, osteoblasts, arterial smooth muscle cells and brain glial cells. The PDGF-1(A) homodimer binds only to its specific receptor alpha, and the hPDGF heterodimer and PDGF-2(B) homodimer bind to both receptors a and b. In addition to their mitogenic action, PDGF stimulates important cellular metabolic activities, including protein, lipid and prostaglandin synthesis. It appears to be an important factor in early development and in vivo appears to modulate tissue regeneration and remodelling during wound healing and osteogenesis. The inappropriate expression of PDGF genes and their mitogenic products has been linked to several proliferative disorders such as fibrosis, atherosclerosis and neoplasia.