Platelet-derived growth factor and its role in health and disease

Abstract

Platelet-derived growth factor (PDGF) was first discovered in platelets because they are the principal source of mitogenic activity in whole blood serum for mesenchymal cells in culture. PDGF is ubiquitous in that it can be formed by a large number of normal cells as well as many varieties of transformed cells. However, its expression and biological activity appear to be controlled at a number of different levels. The molecule consists of two peptide chains (termed 'A' and 'B') and is found as one of at least three possible isoforms, (AB, AA or BB). Each of these isoforms binds to a high-affinity cell-surface receptor that is composed of two different subunits, each of which has specificity for one or the other of the peptide chains of PDGF. The two receptor subunits are present in differing amounts on different cell types, and therefore the capacity of the different isoforms of PDGF to induce mitogenesis depends on the specific PDGF isoform and the relative numbers of receptor subunits present on the responding cell. In addition to inducing cell replication, PDGF elicits a number of intracellular signals related to mitogenesis, is chemotactic, is a vasoconstrictor, activates leukocytes, and modulates extracellular matrix turnover. This growth factor is probably involved in a number of biologically important events including wound repair, embryogenesis and development, and inflammation, leading to fibrosis, atherosclerosis and neoplasia.

Platelet-derived Growth Factor Differentially Regulates the Expression and Post-translational Modification of Versican by Arterial Smooth Muscle Cells through Distinct Protein Kinase C and Extracellular Signal-regulated Kinase Pathways

“…These results support the observations in Fig. 2, suggesting that the increases observed in We have previously demonstrated that the expression of versican in these cells is genistein-sensitive (15) and thus thought to be linked via the PDGF signaling pathway most closely associated with the mitogenic action of PDGF (40). We therefore investigated the effect of inhibiting ERK activation on PDGFmediated versican mRNA expression.…”

Ca(2+)-channel blockers modulate expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and low density lipoprotein receptor genes stimulated by platelet-derived growth factor.

“…PDGF has numerous biological properties; among these are potent mitogenic, chemotactic, and vasoconstrictor effects on vascular smooth muscle cells (VSMC) (2). Ross et al (3) have reported that various PDGF isoforms have unique expressions in different cell types that are involved in development of atherosclerotic lesions.…”

Maternal Plasma and Amniotic Fluid Cytokines in Monochorionic, Diamniotic Twin Pregnancies Complicated by Twin-to-Twin Transfusion Syndrome

“…Only 2 cytokine-related markers showed significant differences when uncomplicated MC and DC twins were compared with MC twins complicated by TTTS, namely PDGF-BB and TIMP-1. PDGF-BB is known to have a role in regulating cell growth and division [26] as well as vessel stabilisation [27] and was higher in twins with a DC placenta than those with an MC placenta (DC > TTTS > uncomplicated MC). An increase in PDGF-BB has been observed in pregnancy-induced hypertension in association with diminished vascular remodelling [27].…”

“…The sensitivity of all assays ranged between 3.04 and 15.2 pg/ml, and these values were utilised if the assay result was outside the reference range. The methodology has previously been described in detail elsewhere [26,27,28]. All assays were performed by C.E.F.…”