Muscular proteomic profiling of deep pressure ulcers reveals myoprotective role of JAK2 in ischemia and reperfusion injury.

Pressure ulcers (PUs) are a complex and serious clinical problem. Deep tissue injury (DTI) is either the outcome or the trigger of deep PUs. However, the cellular and molecular mechanisms that contribute to the pathogenesis of deep PUs remain unclear. In this study, the degeneration characteristics and increased autophagy and apoptosis were observed in deep PU muscle tissues. Muscular proteome of deep PU revealed that a total of 520 proteins were differentially expressed, particularly, JAK2 was down-regulated. Intriguingly, expression of JAK2 in C2C12 myoblasts exposed to oxygen-glucose deprivation and reoxygenation (OGD/R) insult was also distinctly reduced. Ex vivo, we transfected C2C12 myoblasts with lentivirus carrying the JAK2 plasmid and found that JAK2-overexpressed myoblasts exhibited a decrease in autophagy and apoptosis after OGD/R treatment, as well as less cell death. Finally, Western blot analysis determined that p-JAK2, p-AKT, p-mTOR and p-ERK1/2 levels were significantly elevated, accompanied by JAK2 overexpression but without p-STAT3, and inhibition of the AKT and ERK1/2 pathway resulted in elevated apoptosis and/or autophagy. These results demonstrated that JAK2 may play an important protective role in muscular ischemia and reperfusion injury during DTI development by inhibition of autophagy and apoptosis through the AKT and ERK1/2 pathways.