骨骼肌
生物
细胞生物学
再生(生物学)
心肌细胞
细胞内
调节器
内分泌学
生物化学
基因
作者
Zhiyuan Sun,Xiuying Shan,Chun’e Fan,Lutao Liu,Shuai Li,Jiahui Wang,Na Zhou,Min–Sheng Zhu,Huaqun Chen
出处
期刊:Stem Cells
[Oxford University Press]
日期:2024-08-04
标识
DOI:10.1093/stmcls/sxae048
摘要
Abstract It has been documented that caspase 3 activity is necessary for skeletal muscle regeneration, but how its activity is regulated is largely unknown. Our previous report shows that intracellular TMEM16A, a calcium activated chloride channel, significantly regulates caspase 3 activity in myoblasts during skeletal muscle development. By using a mouse line with satellite cell (SC)-specific deletion of TMEM16A, we examined the role of TMEM16A in regulating caspase 3 activity in SC (or SC-derived myoblast) as well as skeletal muscle regeneration. The mutant animals displayed apparently impaired regeneration capacity in adult muscle along with enhanced ER stress and elevated caspase 3 activity in Tmem16a-/- SC derived myoblasts. Blockade of either excessive ER stress or caspase 3 activity by small molecules significantly restored the inhibited myogenic differentiation of Tmem16a-/- SCs, indicating that excessive caspase 3 activity resulted from TMEM16A deletion contributes to the impaired muscle regeneration and the upstream regulator of caspase 3 was ER stress. Our results revealed an essential role of TMEM16A in satellite cell mediated skeletal muscle regeneration by ensuring a moderate level of caspase 3 activity.
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