Myonuclear apoptosis via cleaved caspase‐3 upregulation is related to macrophage accumulation underlying immobilization‐induced muscle fibrosis
Myonuclear apoptosis via cleaved caspase‐3 upregulation is related to macrophage accumulation underlying immobilization‐induced muscle fibrosis
复制标题
通过裂解的 caspase-3 上调引起的肌核细胞凋亡与固定诱导的肌肉纤维化背后的巨噬细胞积累有关
DOI：
10.1002/mus.27473
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发表时间：
2021
期刊：
影响因子：
3.4
通讯作者：
Okita M
中科院分区：
文献类型：
--
作者：
Tanaka N;Honda Y;Kajiwara Y;Kataoka H;Origuchi T;Sakamoto J;Okita M
引言/目的虽然巨噬细胞积聚在制动诱导的肌肉纤维化的发展中起着关键作用，但其潜在机制仍不清楚。因此，我们将重点放在通过切割caspase-3的肌细胞凋亡的改变，并研究这些变化是否可能与巨噬细胞积聚有关。结果制动组大鼠比目鱼肌胶原mRNA和蛋白表达及CD 11b阳性细胞数均显著高于对照组大鼠在1周和2周。1周和2周对照大鼠中TdT介导的dUTP缺口末端标记（TUNEL）阳性肌核计数分别为0.2 ± 0.1和0.2 ± 0.5，而1周和2周固定大鼠中分别为1.0 ± 0.6和1.1 ± 0.5。1周和2周对照组大鼠的裂解caspase-3蛋白表达为0.2 ± 0.1和0.2 ± 0.1，而1周和2周制动组大鼠的裂解caspase-3蛋白表达为0.5 ± 0.1和0.4 ± 0.2。在1周和2周时，固定大鼠的TUNEL阳性肌细胞核计数和裂解的caspase-3蛋白表达显著高于对照大鼠。1周和2周对照大鼠的肌核数量分别为2.8 ± 0.1和2.6 ± 0.4，而1周和2周固定大鼠的肌核数量分别为2.2 ± 0.4和2.2 ± 0.2。在两个时间点，制动组的肌细胞核数量均显著低于对照组大鼠。DiscussionMycobacterium凋亡通过上调裂解的caspase-3可能诱导巨噬细胞积聚。这些变化与制动诱导的肌肉纤维化有关。
Introduction/AimsAlthough macrophage accumulation plays a key role in the development of immobilization‐induced muscle fibrosis, the underlying mechanisms remain unclear. Therefore, we focused on the alterations of myonuclear apoptosis via cleaved caspase‐3, and investigated whether these changes may be related to macrophage accumulation.MethodsEight‐week‐old Wistar rats were divided into immobilization and control groups, and the soleus muscles were selected for analysis.ResultsThe mRNA and protein expression of collagen and the number of CD11b‐positive cells were significantly higher in the immobilized rats than in the control rats at 1 and 2 weeks. TdT‐mediated dUTP nick end‐labeling (TUNEL)‐positive myonuclei counts in 1‐ and 2‐week control rats were 0.2 ± 0.1 and 0.2 ± 0.5, whereas they were 1.0 ± 0.6 and 1.1 ± 0.5 in 1‐ and 2‐week immobilized rats. The cleaved caspase‐3 protein expressions in 1‐ and 2‐week control rats were 0.2 ± 0.1 and 0.2 ± 0.1, whereas they were 0.5 ± 0.1 and 0.4 ± 0.2 in 1‐ and 2‐week immobilized rats. TUNEL‐positive myonuclei counts and cleaved caspase‐3 protein expression were significantly higher in immobilized rats than in control rats at 1 and 2 weeks. The numbers of myonuclei in 1‐ and 2‐week control rats were 2.8 ± 0.1 and 2.6 ± 0.4, whereas they were 2.2 ± 0.4 and 2.2 ± 0.2 in 1‐ and 2‐week immobilized rats. The numbers of myonuclei were significantly lower in immobilized than in control rats at both time‐points.DiscussionMyonuclear apoptosis via the upregulation of cleaved caspase‐3 might induce macrophage accumulation. These alterations are related to immobilization‐induced muscle fibrosis.
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