Heat Shock Protein 90 Versus Conventional Growth Factors in Acute and Diabetic Wound Healing

Abstract

Diabetic foot lesions are responsible for more hospitalizations than any other complication of diabetes in the United States of America. The number of diabetic foot ulcer-caused lower limb amputations is approaching 100,000/year, a rapid increase due to an aging population and the rising incidence of obesity. Cost-effect treatments are currently limited. For decades, the conventional wisdom is that growth factors constitute the driving forces of wound healing. Therefore, more than 30 growth factors have been extensively studied in animal models and a dozen of these growth factors have been subjected to clinical trials. Only PDGF-BB received the US FDA approval for treatment of diabetic ulcers in 1997. However, the modest efficacy, high cost and risks of causing cancer by PDGF-BB (becaplermin gel) have limited its use in clinical practice. This reality continues to be overlooked or ignored. An unconventional wound-healing molecule, extracellular heat shock protein-90alpha (eHsp90α), has recently been reported. Unlike restricted cell type specificity of PDGF-BB, eHsp90α is a common pro-motility factor of all skin cells, eHsp90α also overrides TGFβ inhibition and hyperglycemia. Topical application of eHsp90α accelerated both acute and diabetic wound closure far more effectively than PDGF-BB. We discuss what makes Hsp90α superior to conventional growth factors in wound healing.