Plateletderived growth factor

PDGF is a polypeptide growth factor that is sometimes termed osteosarcoma-derived growth factor or glioma-derived growth factor. It was first identified over 20 years ago as being the major growth factor synthesized by platelets. It is also produced by a variety of cell types. PDGF exhibits a mitogenic effect on fibroblasts, smooth muscle cells and glial cells, and exerts various additional biological activities (Table 10.11).

PDGF plays an important role in the wound healing process. It is released at the site of damage by activated platelets, and acts as a mitogen/chemoattractant for many of the cells responsible for initiation of tissue repair. It thus tends to act primarily in a paracrine manner. It also represents an autocrine/paracrine growth factor for a variety of malignant cells.

Active PDGF is a dimer. Two constituent polypeptides, A and B, have been identified, and three active PDGF isoforms are possible: AA, BB and AB. Two slightly different isoforms of the human PDGF A polypeptide (generated by differential mRNA splicing) have been identified. The short A form contains 110 amino acids and the long form contains 125 amino acids. Both exhibit one potential glycosylation site and three intrachain disulfide bonds. Two PDGF receptor subunits have been identified. Both are transmembrane glycoproteins whose cytoplasmic domains display tyrosine kinase activity upon activation.

In vitro and in vivo studies support the thesis that PDGF is of value in wound management, particularly with regard to chronic wounds. All three isoforms of PDGF are available from a range of recombinant systems. In vitro studies, using various cell lines, suggest that PDGF AB or BB dimeric isoforms are the most potent.

Normal skin appears to be devoid of PDGF receptors. Animal studies illustrate that rapid expression of both a and P receptor subunits is induced upon generation of an experimental wound (e.g. a surgical incision). Receptor expression is again switched off following re-epithelialization and complete healing of the wound.

Initial human trials have found that daily topical application of PDGF (BB isoform) stimulated higher healing rates of chronic pressure wounds, although the improvement recorded fell just short of being statistically significant. A second trial found that daily topical application of PDGF (BB) did promote statistically significant accelerated healing rates of chronic diabetic ulcers. The product (tradename Regranex) was approved for general medical use in the late 1990s. Its active ingredient is manufactured by Chiron Corporation, in an engineered strain of Saccharomycies cerevisiae harbouring the PDGF B chain gene. Regranex is notable in that it is formulated as a non-sterile (low bioburden) gel, destined for topical administration. The final formulation contains methylparaben, propylparaben and m-cresol as preservatives. In addition, as is the case with EGF, PDGF antagonists may also prove valuable in the treatment of some cancer types in which inappropriately high generation of PDGF-like mitogenic signals leads to the transformed state.

How To Have Beutiful Non Aging Skin

How To Have Beutiful Non Aging Skin

Age does a lot of things to us and most of them arent good. Sure, we may get wiser, and more knowledgeable as a result of our experiences over time, but time also takes a hefty toll on our health, and appearance.

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