Gastrocnemius muscle-Deletion of TECRL promotes skeletal muscle repair

Myogenic regeneration relies on the proliferation and differentiation of satellite cells. TECRL (Trans-2,3-Enoyl-CoA Reductase Like) is an endoplasmic reticulum protein only expressed in cardiac and skeletal muscle. However, its role in myogenesis remains unknown. We show that TECRL expression is increased in response to ischemic injury. Satellite cell-specific deletion of TECRL enhances muscle repair by increasing the expression of EGR2 through the activation of the ERK1/2 signaling pathway, which in turn promotes the expression of PAX7. We further showed that TECRL deletion led to the upregulation of the histone acetyltransferase general control non-derepressible 5 (GCN5), which enhances the transcription of EGR2 through acetylation. Total RNA from TECRLflox/flox and TECRLscko gastrocnemius muscle. TECRLscko mice (satellite cell specific TECRL knockout mice) were generated by crossing Pax7-Cre mice (Stock Number: 010530, Pax7tm1 (cre) Mrc/J; The Jackson Laboratory, Bar Harbor, ME) with TECRLflox/flox mice (generated by Cyagen, Guangzhou, China).肌源性再生依赖于卫星细胞的增殖与分化。Trans-2,3-烯酰辅酶A还原酶样蛋白（Trans-2,3-Enoyl-CoA Reductase Like，TECRL）是一种仅在心肌和骨骼肌中表达的内质网蛋白，但其在肌发生过程中的功能仍未明确。本研究发现，TECRL的表达会在缺血性损伤刺激下上调。卫星细胞特异性敲除TECRL可通过激活ERK1/2信号通路上调早期生长反应因子2（EGR2）的表达，进而促进配对盒蛋白7（PAX7）的表达，最终增强肌肉修复能力。本研究进一步证实，TECRL敲除会导致组蛋白乙酰转移酶通用控制非阻遏蛋白5（GCN5）的表达上调，后者可通过乙酰化修饰增强EGR2的转录活性。实验所用总RNA取自TECRL flox/flox纯合小鼠与卫星细胞特异性TECRL敲除（TECRLscko）小鼠的腓肠肌。TECRLscko小鼠（即卫星细胞特异性TECRL敲除小鼠）通过将Pax7-Cre工具小鼠（品系编号：010530，Pax7tm1(cre)Mrc/J；美国杰克逊实验室，缅因州巴港）与TECRL flox/flox纯合小鼠（由中国广州赛业生物构建）杂交获得。