Inhibition of SGK3 regulates hyperplastic scar development in rats through the MAPK/ERK signaling pathway.

Abstract

Hypertrophic scars (HS) frequently result from severe burns, surgical procedures and other causes of deep skin damage. The impact of serum/glucocorticoid regulated kinase family member 3 (SGK3) on the formation of HS remains unclear. HS model rats were constructed by the scalding method. In addition, tissue samples from clinical patients were collected to detect the SGK3 levels in normal skin and HS tissues by RT-qPCR and western blotting. Human-derived HS fibroblasts (HSFBs) were isolated and identified using immunofluorescence. Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine staining and scratch assays were applied to test the ability of the HSFBs to proliferate and migrate. The influence of an SGK3 inhibitor on wound healing in rats was assessed using hematoxylin and eosin staining, Masson staining, immunofluorescence and immunohistochemistry. In addition, the levels of collagen and the proteins involved in the mitogen-activated protein kinase (MAPK)/extracellular regulated protein kinase (ERK) pathway were measured by western blotting. SGK3 was highly expressed in HS tissues. Knockdown of SGK3 resulted in reduced SGK3 levels in HSFBs. Knockdown of SGK3 reduced the proliferation and migration ability of HSFBs and suppressed cellular fibrosis. Injection with an SGK3 inhibitor reduced the burn scar area, decreased epithelial thickness and inhibited collagen deposition in rats. This inhibitor also resulted in the downregulation of collagen and MAPK/ERK pathway-related proteins. In addition, MAPK/ERK pathway agonists attenuated the effect of SGK3 inhibition, promoting HS formation while inhibiting wound healing in rats; however, MAPK inhibitors had the opposite effect. In conclusion, inhibition of SGK3 reduces the proliferation, migration and fibrosis abilities of HSFBs as well as promotes wound healing and inhibits HS formation in rats by downregulating the MAPK/ERK pathway.