Analysis of muscular proteomics of deep pressure ulcers reveals JAK2 influence on muscle autophagy and apoptosis

ABSTRACT: Pressure ulcers (PU) is a complex and serious clinical problem. Deep tissue injury is either the outcome or the trigger of deep PU. However, the cellular and molecular mechanisms that contribute to the pathogenesis of deep PU remain unclear. In this study, the degeneration characteristics, increased autophagy and apoptosis were observed in deep PU muscle tissues by H&E staining, transmission electron microscope, TUNEL staining and western blot analysis. We further conducted quantitative liquid chromatography-tandem mass spectrometry analysis to explore the proteome of deep PU muscle, a total of 520 proteins were differently expressed, including 427 up-regulated and 93 down-regulated. In particular, downregulation was observed for Janus Kinase 2 (JAK2). Intriguingly, we showed that a distinctly reduced expression of JAK2 in C2C12 myoblasts exposed to oxygen-glucose deprivation and reoxygenation insult. Ex vivo, JAK2 overexpressed myoblasts exhibited decrease of autophagy and apoptosis with the same treatment, along with less cell death. Finally, western blot analysis determined that p-JAK2, p-PI3K, p-AKT, p-mTOR and p-ERK1/2 were significantly elevated, accompanied by JAK2 overexpression, but without p-STAT3. In conclusion, these results demonstrated that both autophagy and apoptosis involve in muscle damage of deep PU, and JAK2 may play an important protective role in muscular ischemia and reperfusion injury by activating AKT and ERK1/2 pathway to inhibit autophagy and apoptosis.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Muscle

SUBMITTER: xiaomei li  

LAB HEAD: Pihong Zhang, Zan Liu,Licheng Ren, Xu Cui, Le Guo, Bimei Jiang, Jie Zhou, Pengfei Liang, Jizhang Zeng, Zhiyou He

PROVIDER: PXD009512 | Pride | 2019-11-12

REPOSITORIES: Pride