| First Author | Young LV | Year | 2021 |
| Journal | Am J Physiol Cell Physiol | Volume | 321 |
| Issue | 1 | Pages | C94-C103 |
| PubMed ID | 33979211 | Mgi Jnum | J:312130 |
| Mgi Id | MGI:6720717 | Doi | 10.1152/ajpcell.00397.2020 |
| Citation | Young LV, et al. (2021) Loss of dystrophin expression in skeletal muscle is associated with senescence of macrophages and endothelial cells. Am J Physiol Cell Physiol 321(1):C94-C103 |
| abstractText | Cellular senescence is the irreversible arrest of normally dividing cells and is driven by cell cycle inhibitory proteins such as p16, p21, and p53. When cells enter senescence, they secrete a host of proinflammatory factors known as the senescence-associated secretory phenotype, which has deleterious effects on surrounding cells and tissues. Little is known of the role of senescence in Duchenne muscular dystrophy (DMD), the fatal X-linked neuromuscular disorder typified by chronic inflammation, extracellular matrix remodeling, and a progressive loss in muscle mass and function. Here, we demonstrate using C57-mdx (8-wk-old) and D2-mdx (4-wk-old and 8-wk-old) mice, two mouse models of DMD, that cells displaying canonical markers of senescence are found within the skeletal muscle. Eight-week-old D2-mdx mice, which display severe muscle pathology, had greater numbers of senescent cells associated with areas of inflammation, which were mostly Cdkn1a-positive macrophages, whereas in C57-mdx muscle, senescent populations were endothelial cells and macrophages localized to newly regenerated myofibers. Interestingly, this pattern was similar to cardiotoxin (CTX)-injured wild-type (WT) muscle, which experienced a transient senescent response. Dystrophic muscle demonstrated significant upregulations in senescence pathway genes [Cdkn1a (p21), Cdkn2a (p16(INK4A)), and Trp53 (p53)], which correlated with the quantity of senescence-associated beta-galactosidase (SA-beta-Gal)-positive cells. These results highlight an underexplored role for cellular senescence in murine dystrophic muscle. |
