Heat-shock protein 72/73 and impaired wound healing in diabetic and hypercortisolemic states

Background. Impaired wound healing is a well-documented phenomenon in exper imental and clinical diabetes. Emerging evidence favors the involvement of glucocorticoids (GCs) in the pathogenesis of this diabetic complication. Re cent data indicated that a heat-shock protein (HSP) with a molecular weight of about 70 hd is expressed in wound healing and it is under the control o f the hypothalamic-pituitary-adrenal axis. In view of these findings, the c urrent study was designed to examine the influence of diabetes and the hype rcortisolemic state on the expression of HSP 72/73 during wound healing. Methods. Induction of diabetes was achieved by the intravenous injection of streptozotocin at a dose of 55 mg/kg: Subcutaneously implanted polyvinyl a lcohol (PVA) sponges were used as a wound healing model. Control and diabet ic animals received respectively, subcutaneous 30-day timed-release pellets of GC (200 mg) and RU 486 (25 mg). Corresponding animal received placebo p ellets. Expression of HSP 72/73 within the PVA sponges was assayed with use of Western blotting and immunohistochemical techniques. Results, GCs caused a Gushing-like syndrome with weight loss and adrenal at rophy. A pronounced accumulation of constitutive HSP 72/73 was observed in the cytoplasm of various cell types including fibroblasts, macrophages, and endothelium of nondiabetic controls. The PVA sponge contents of HSP 72/73 were decreased as a function of diabetes. A similar phenomenon was seen in control animals receiving high doses of GCs. Partial normalization of the a ssociated hyperglycemic and hypercortisolemic dates of diabetes with insuli n (hyperglycemia) and the GG receptor block RU 486 (hypercortisolemia) amel iorated the diabetes-related decrease in PVA sponge contents of HSP 72/73. Conclusions, The current study provides evidence that both diabetes and the hypercortisolemic state are associated with a reduction in PVA sponge cont ent of HSP 72/73. An amelioration of these changes was achieved by the inst itution of RU 486 therapy. Although our data may point to the possibility t hat the diabetes-related decrease in HSP 72/73 is mediated at least in part by GCs, a confirmation regarding this premise awaits further investigation .