title: Calpain 3 Expression Pattern during Gastrocnemius Muscle Atrophy and Regeneration Following Sciatic Nerve Injury in Rats.
abstract: Calpain 3 (CAPN3), also known as p94, is a skeletal muscle-specific member of the calpain family that is involved in muscular dystrophy; however, the roles of CAPN3 in muscular atrophy and regeneration are yet to be understood. In the present study, we attempted to explain the effect of CAPN3 in muscle atrophy by evaluating CAPN3 expression in rat gastrocnemius muscle following reversible sciatic nerve injury. After nerve injury, the wet weight ratio and cross sectional area (CSA) of gastrocnemius muscle were decreased gradually from 1-14 days and then recovery from 14-28 days. The active form of CAPN3 (~62 kDa) protein decreased slightly on day 3 and then increased from day 7 to 14 before a decrease from day 14 to 28. The result of linear correlation analysis showed that expression of the active CAPN3 protein level was negatively correlated with muscle wet weight ratio. CAPN3 knockdown by short interfering RNA (siRNA) injection improved muscle recovery on days 7 and 14 after injury as compared to that observed with control siRNA treatment. Depletion of CAPN3 gene expression could promote myoblast differentiation in L6 cells. Based on these findings, we conclude that the expression pattern of the active CAPN3 protein is linked to muscle atrophy and regeneration following denervation: its upregulation during early stages may promote satellite cell renewal by inhibiting differentiation, whereas in later stages, CAPN3 expression may be downregulated to stimulate myogenic differentiation and enhance recovery. These results provide a novel mechanistic insight into the role of CAPN3 protein in muscle regeneration after peripheral nerve injury.
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China. wuronghua5@ntu.edu.cn.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Wu
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China. 13510003@yjs.ntu.edu.cn.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Histology and Embryology, Medical College, Nantong University, Nantong 226001, China. yjshz@ntu.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Yao
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China. liuyan@ntu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, the Affiliated Hospital of Nantong University, Nantong 226001, China. tdfyywc@163.com.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China. liumei@ntu.edu.cn.
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
mesh_terms: D000818:Animals; D002154:Calpain / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009133:Muscular Atrophy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D017570:MyoD Protein / Q000235:genetics; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D059348:Peripheral Nerve Injuries / Q000150:complications / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D012038:Regeneration; D020426:Sciatic Neuropathy / Q000150:complications / Q000235:genetics*
chemical_list: D007527:Isoenzymes; D009124:Muscle Proteins; D017570:MyoD Protein; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D002154:Calpain; C491372:Capn3 protein, rat
keywords: Calpain 3 (CAPN3); gastrocnemius muscle; myoblast differentiation; rat; sciatic nerve injury