{Reference Type}: Journal Article
{Title}: TMEM16A regulates satellite cell mediated skeletal muscle regeneration by ensuring a moderate level of caspase 3 activity.
{Author}: Sun Z;Shan X;Fan C;Liu L;Li S;Wang J;Zhou N;Zhu M;Chen H;
{Journal}: Stem Cells
{Volume}: 0
{Issue}: 0
{Year}: 2024 Aug 4
{Factor}: 5.845
{DOI}: 10.1093/stmcls/sxae048
{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.