Platelet-derived growth factor (PDGF) is a family of dimeric ligands that bind to and activate two cell surface receptor tyrosine kinase subunits, PDGFRa and PDGFRp. Four different ligand chains (PDGF-A, B, C and D) assemble into five different dimeric combinations (AA, AB, BB, CC and DD). Binding of bivalent ligands leads to receptor subunit dimerization. The apposition of the receptor kinase domains leads to reciprocal receptor subunit phosphoryla-tion, further activating the tyrosine kinases and creating docking sites for down-stream signal transducers.
One of the first biological functions demonstrated for PDGF was its mitogenic activity on cultured vascular smooth muscle cells (vSMC) . The PDGF preparations used for these early studier were derived from platelets and consisted mainly of PDGF-AB heterodimers. Subsequently it was demonstrated that vSMC carry both PDGFRP and PDGFRa. In vitro studies also demonstrated that cultured vascular endothelial cells produce PDGF A and B. Thus, early in vitro findings provided indications that PDGFs and their receptors play a role in the vasculature. However, the focus was placed on large vessels and the potential function of PDGF as a "wound healing" hormone for the vascular wall and surrounding connective tissue. For example, PDGF was suggested to be of central importance in the "response to injury" model of atherosclerosis championed by Russell Ross and co-workers.
Subsequent in vitro studies argued for PDGF signaling to have a role also in the microvasculature. In co-culture studies, endothelial cells promoted pericyte migration—a function that was attributed to PDGF. Moreover, pericyte contact with the endothelial cells inhibited proliferation of the latter, and TGFb was implicated in this function [2, 3].
Was this article helpful?
This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.