Ablation of Bax and Bak protects skeletal muscle against pressure-induced injury

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...

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Published inScientific reports Vol. 8; no. 1; pp. 3689 - 11
Main Authors Tam, Bjorn T., Yu, Angus P., Tam, Eric W., Monks, Douglas A., Wang, Xu P., Pei, Xiao M., Koh, Su P., Sin, Thomas K., Law, Helen K. W., Ugwu, Felix N., Supriya, Rashmi, Yung, Benjamin Y., Yip, Shea P., Wong, S. C., Chan, Lawrence W., Lai, Christopher W., Ouyang, Pin, Siu, Parco M.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 27.02.2018
Nature Publishing Group
Subjects
13/2
631/443
64/110
692/699
AKT protein
Apoptosis
Autophagy
BNIP3 protein
Compression
Humanities and Social Sciences
Ischemia
Mitochondria
multidisciplinary
Musculoskeletal system
Phagocytosis
Pressure
Pressure ulcers
Reperfusion
Science
Science (multidisciplinary)
Skeletal muscle
Skin
Therapeutic applications
TOR protein
Unloading
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Summary: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.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-21853-5