PDGF, also known as a Platelet-derived growth factor, is one of many growth factors that regulate cell division and growth within the body. Specifically, PDGF plays a vital role in the formation of blood vessels, a process also known as angiogenesis, which is the growth of blood vessels from blood vessel tissue that already exists. This process can include mitogenesis, such as proliferation of mesenchymal cells, like fibroblasts, osteoblasts, tenocytes, vascular smooth muscle cells, and mesenchymal stem cells, in addition to chemotaxis, which is the planned migration of mesenchymal cells. While PDGF is a dimeric glycoprotein that can be made up of two A sub-units and two B sub-units or one of each group of sub-units.
PDGF is a mitogen that is potent for cells of mesenchymal origin, which includes fibroblasts, smooth muscle cells, and glial cells. For both mice and humans, the signalling network that PDGF uses is made up of five ligands, PDGF-AA through to -DD, and two receptors - these are PDGFRalpha and PDGFRbeta. All PDGF functions are produced, disulphide-linked homodimers, but only PDGFA and B can form working, functional heterodimers.
Although PDGF is synthesized, stored, and released by platelets upon their activation, it can also be produced by other cells; this includes smooth muscle cells, activated macrophages, and endothelial cells. In medicine, recombinant PDGF can be used to help chronic ulcers to heal, as well as in orthopaedic surgery and periodontics, as an alternative to a bone autograft to stimulate bone regeneration and repair.
Known as the receptor for PDGF, PDGFR is known as a receptor tyrosine kinase or RTK, which is a type of cell surface receptor. There are two types of PDGFRs that have been identified; these are alpha and beta-type PDGFRs. The alpha type is able to bind with PDGF-BB and PDGF-AB, whereas the beta type PDGFR can bind with high-affinity PDGFR-BB and PDGF-AB. How it works is that PDGFR ligend binds within the second and third immunoglobulin domains. Upon activation by PDGF, the receptors dimerise and are ‘turned on’ by autophosphorylation on sites within their cytosolic domains. These can be used to monitor binding of cofactors and activate signal transduction. For instance, this can happen via the P13K pathway or via reactive oxygen species (ROS).
Further downstream from this, the effects include regulation of gene expression and also the cell cycle. Various studies have been performed on the role of P13K. Data suggests that while the molecule tends to be part of the growth signalling complex, it does play a more significant role in controlling the migration of cells.
The various ligend isoforms have a range of variable affinities for the receptors of isoforms, and these may vary from hetero or homo-dimers. This leads to specificity of downstream signalling, which has been shown that sis oncogene is derived from the PDGF B-chain gene. Studies have shown that PDGF-BB is the highest affinity ligand for PDGF-beta. It has also been suggested that PDGF-beta is a key marker for hepatic stellate cell activation in the fibrogenesis process.