期刊
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
卷 321, 期 1, 页码 C94-C103出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00397.2020
关键词
Duchenne muscular dystrophy; muscle; regeneration; SASP; senescence
资金
- Natural Sciences and Engineering Research Council of Canada [RGPIN-2016-05747]
The study found the presence of cells with canonical markers of senescence in mouse models of Duchenne muscular dystrophy, particularly with more senescent cells associated with areas of inflammation in 8-week-old D2-mdx mice. These results provide new insights into the role of cellular senescence in dystrophic muscle.
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 (p16INK4A), and Trp53 (p53)], which correlated with the quantity of senescence-associated 13-galactosidase (SA -13-Gal)-positive cells. These results highlight an underexplored role for cellular senescence in murine dystrophic muscle.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据