Effect of sarcolipin-mediated cell transdifferentiation in sarcopenia-associated skeletal muscle fibrosis
Effect of sarcolipin-mediated cell transdifferentiation in sarcopenia-associated skeletal muscle fibrosis
复制标题
肌磷脂介导的细胞转分化对肌少症相关骨骼肌纤维化的影响
DOI：
10.1016/j.yexcr.2020.111890
复制
发表时间：
2020-04-01
影响因子：
3.7
通讯作者：
Xiao, Qian
中科院分区：
文献类型：
--
作者：
Chen, Qiu-Nan;Fan, Zhen;Xiao, Qian
纤维化是肌肉老化过程中一个关键的病理事件，加速了肌肉减少症的发展。我们发现肌磷脂（SLN）在衰老过程中高度表达，促进细胞内钙超载并参与受损的肌分化。用d -半乳糖（D-gal）诱导C2C12成肌细胞衰老。采用常规aav介导的SLN敲低细胞，研究SLN在肌肉生理和病理生理中的作用。用D-gal处理C2C12细胞，可促进纤维化和SLN上调。参与肌原性转分化的tgf - β 1和α - sma的表达也升高。肌磷脂表达减少的C2C12细胞产生的胶原蛋白量减少。我们的研究发现，在与衰老相关的骨骼肌细胞纤维化过程中，SLN在调节肌源性转分化中的作用尚未被认识。靶向SLN可能是缓解肌肉减少症相关肌肉纤维化的一种新的治疗策略。
Fibrosis is a key pathological event during muscle aging that accelerates the development of sarcopenia. We show that sarcolipin (SLN) is highly expressed during aging, promotes intracellular calcium overload and participates in impaired myogenic differentiation. D-Galactose (D-gal) was used to induce senescence in C2C12 myoblasts. Conventional AAV-mediated SLN knockdown cells were used to study the role of SLN in muscle physiology and pathophysiology. C2C12 cells were treated with D-gal, which promoted fibrosis and SLN upregulation. The expression of TGF-beta 1 and alpha-SMA, which participate in myogenic transdifferentiation, were also elevated. C2C12 cells with reduced sarcolipin expression produced decreased amounts of collagen. Our study identified an unrecognized role of SLN in regulating myogenic transdifferentiation during aging-associated skeletal muscle cell fibrosis. Targeting SLN may be a novel therapeutic strategy to relieve sarcopenia-associated muscle fibrosis.