Wu Ronghua, Yan Yingying, Yao Jian, Liu Yan, Zhao Jianmei, Liu Mei
Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
Department of Histology and Embryology, Medical College, Nantong University, Nantong 226001, China.
Int J Mol Sci. 2015 Nov 11;16(11):26927-35. doi: 10.3390/ijms161126003.
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.
钙蛋白酶3（CAPN3），也被称为p94，是钙蛋白酶家族中骨骼肌特异性成员，与肌肉萎缩症有关；然而，CAPN3在肌肉萎缩和再生中的作用尚不清楚。在本研究中，我们试图通过评估可逆性坐骨神经损伤后大鼠腓肠肌中CAPN3的表达来解释CAPN3在肌肉萎缩中的作用。神经损伤后，腓肠肌的湿重比和横截面积（CSA）在1至14天逐渐降低，然后在14至28天恢复。CAPN3的活性形式（约62 kDa）蛋白在第3天略有下降，然后从第7天到第14天增加，之后从第14天到第28天下降。线性相关分析结果表明，活性CAPN3蛋白水平的表达与肌肉湿重比呈负相关。与对照siRNA处理相比，通过注射短干扰RNA（siRNA）敲低CAPN3可改善损伤后第7天和第14天的肌肉恢复。CAPN3基因表达的缺失可促进L6细胞中的成肌细胞分化。基于这些发现，我们得出结论，活性CAPN3蛋白的表达模式与去神经支配后的肌肉萎缩和再生有关：其在早期阶段的上调可能通过抑制分化促进卫星细胞更新，而在后期阶段，CAPN3表达可能下调以刺激肌源性分化并增强恢复。这些结果为CAPN3蛋白在周围神经损伤后肌肉再生中的作用提供了新的机制性见解。
