Calpain 3 Expression Pattern during Gastrocnemius Muscle Atrophy and Regeneration Following Sciatic Nerve Injury in Rats.
Calpain 3 Expression Pattern during Gastrocnemius Muscle Atrophy and Regeneration Following Sciatic Nerve Injury in Rats.
复制标题
大鼠坐骨神经损伤后腓肠肌萎缩和再生期间钙蛋白酶 3 的表达模式。
DOI：
10.3390/ijms161126003
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发表时间：
2015-11-11
影响因子：
5.6
通讯作者：
Liu M
中科院分区：
文献类型：
--
作者：
Wu R;Yan Y;Yao J;Liu Y;Zhao J;Liu M
钙蛋白酶3（CAPN 3），也称为p94，是钙蛋白酶家族的骨骼肌特异性成员，参与肌营养不良症;然而，CAPN 3在肌肉萎缩和再生中的作用尚未被理解。在本研究中，我们试图通过评估CAPN 3在大鼠腓肠肌可逆性坐骨神经损伤后的表达来解释CAPN 3在肌肉萎缩中的作用。腓肠肌湿重比和横截面积在神经损伤后1-14天逐渐下降，14-28天恢复正常。CAPN 3（~62 kDa）蛋白的活性形式在第3天略有下降，然后从第7天到第14天增加，然后从第14天到第28天下降。线性相关分析结果表明，CAPN 3活性蛋白表达水平与肌肉湿重比呈负相关。与用对照siRNA治疗观察到的相比，通过短干扰RNA（siRNA）注射的CAPN 3敲低改善了损伤后第7天和第14天的肌肉恢复。CAPN 3基因表达缺失可促进L 6细胞向成肌细胞分化。基于这些发现，我们得出结论，活性CAPN 3蛋白的表达模式与失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，CAPN 3表达可能下调以刺激肌源性分化并增强恢复。这些结果为CAPN 3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见解。
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.