| First Author | Meyer GA | Year | 2022 |
| Journal | Elife | Volume | 11 |
| PubMed ID | 36508247 | Mgi Jnum | J:355084 |
| Mgi Id | MGI:7643643 | Doi | 10.7554/eLife.82016 |
| Citation | Meyer GA, et al. (2022) Tenotomy-induced muscle atrophy is sex-specific and independent of NFkappaB. Elife 11 |
| abstractText | The nuclear factor-kappaB (NFkappaB) pathway is a major thoroughfare for skeletal muscle atrophy and is driven by diverse stimuli. Targeted inhibition of NFkappaB through its canonical mediator IKKbeta effectively mitigates loss of muscle mass across many conditions, from denervation to unloading to cancer. In this study, we used gain- and loss-of-function mouse models to examine the role of NFkappaB in muscle atrophy following rotator cuff tenotomy - a model of chronic rotator cuff tear. IKKbeta was knocked down or constitutively activated in muscle-specific inducible transgenic mice to elicit a twofold gain or loss of NFkappaB signaling. Surprisingly, neither knockdown of IKKbeta nor overexpression of caIKKbeta significantly altered the loss of muscle mass following tenotomy. This finding was consistent across measures of morphological adaptation (fiber cross-sectional area, fiber length, fiber number), tissue pathology (fibrosis and fatty infiltration), and intracellular signaling (ubiquitin-proteasome, autophagy). Intriguingly, late-stage tenotomy-induced atrophy was exacerbated in male mice compared with female mice. This sex specificity was driven by ongoing decreases in fiber cross-sectional area, which paralleled the accumulation of large autophagic vesicles in male, but not female muscle. These findings suggest that tenotomy-induced atrophy is not dependent on NFkappaB and instead may be regulated by autophagy in a sex-specific manner. |
