PDF(Pubmed)
Abstract：
Ubiquitin C-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme originally found in the brain. Our previous work revealed that UCHL1 was also expressed in skeletal muscle and affected myoblast differentiation and metabolism. In this study, we further tested the role of UCHL1 in myogenesis and muscle regeneration following muscle ischemia-reperfusion (IR) injury. In the C2C12 myoblast, UCHL1 knockdown upregulated MyoD and myogenin and promoted myotube formation. The skeletal muscle-specific knockout (smKO) of UCHL1 increased muscle fiber sizes in young mice (1 to 2 months old) but not in adult mice (3 months old). In IR-injured hindlimb muscle, UCHL1 was upregulated. UCHL1 smKO ameliorated tissue damage and injury-induced inflammation. UCHL1 smKO also upregulated myogenic factors and promoted functional recovery in IR injury muscle. Moreover, UCHL1 smKO increased Akt and Pink1/Parkin activities. The overall results suggest that skeletal muscle UCHL1 is a negative factor in skeletal muscle development and recovery following IR injury and therefore is a potential therapeutic target to improve muscle regeneration and functional recovery following injuries.
摘要：
泛素C末端水解酶L1（UCHL1）是最初在大脑中发现的去泛素化酶。我们先前的工作表明，UCHL1也在骨骼肌中表达，并影响成肌细胞的分化和代谢。在这项研究中,我们进一步测试了UCHL1在肌肉缺血再灌注（IR）损伤后的肌生成和肌肉再生中的作用。在C2C12成肌细胞中，UCHL1敲低上调MyoD和肌原蛋白并促进肌管形成。UCHL1的骨骼肌特异性敲除（smKO）增加了年轻小鼠（1至2个月大）的肌纤维大小，但在成年小鼠（3个月大）中没有。在IR损伤的后肢肌肉中，UCHL1上调。UCHL1smKO改善了组织损伤和损伤诱导的炎症。UCHL1smKO还上调肌源性因子并促进IR损伤肌肉的功能恢复。此外，UCHL1smKO增加了Akt和Pink1/Parkin活动。总体结果表明，骨骼肌UCHL1是IR损伤后骨骼肌发育和恢复的负面因素，因此是改善损伤后肌肉再生和功能恢复的潜在治疗靶标。
