Abstract
Pressure-induced injury (PI), such as a pressure ulcer, in patients with limited mobility is a healthcare issue worldwide. PI is an injury to skin and its underlying tissue such as skeletal muscle. Muscle compression, composed of mechanical deformation of muscle and external load, leads to localized ischemia and subsequent unloading reperfusion and, hence, a pressure ulcer in bed-bound patients. Although the gross factors involved in PI have been identified, little is known about the exact disease mechanism or its links to apoptosis, autophagy and inflammation. Here, we report that PI is mediated by intrinsic apoptosis and exacerbated by autophagy. Conditional ablation of Bax and Bak activates the Akt-mTOR pathway and Bnip3-mediated mitophagy and preserves mitochondrial contents in compressed muscle. Moreover, we find that the presence/absence of Bax and Bak alters the roles and functions of autophagy in PI. Our results suggest that manipulating apoptosis and autophagy are potential therapeutic targets for treatment and prevention of PI.
Highlights
Mechanical deformation of muscle by external load leads to localized ischemia and subsequent unloading reperfusion and, a pressure ulcer[1]
To determine whether muscle structural integrity can be maintained by preventing apoptosis, hematoxylin and eosin (H&E) staining was used to assess skeletal muscle morphology
We showed that ablation of Bax and Bak protected skeletal muscle against Pressure-induced injury (PI)
Summary
Mechanical deformation of muscle by external load leads to localized ischemia and subsequent unloading reperfusion and, a pressure ulcer[1]. The highly activated autophagy may have already depleted a significant portion of cellular content, leading to autophagic cell death[7]. It seems that the roles of autophagy in the stressed cells vary depending on the dose, intensity and duration of stress[8]. If there is autophagy activation in cells lacking Bax and Bak, what would be the role and function of autophagy? Would be activated in the absence of apoptosis and the roles of autophagy in skeletal muscle in vivo remains unknown. We examined whether mechanical compression could induce autophagy in skeletal muscle deficient for Bax and Bak
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