Myonuclear apoptosis via cleaved caspase-3 upregulation is related to macrophage accumulation underlying immobilization-induced muscle fibrosis

被引:7
作者
Tanaka, Natsumi [1 ,2 ]
Honda, Yuichiro [1 ,3 ]
Kajiwara, Yasuhiro [1 ,4 ]
Kataoka, Hideki [1 ,5 ]
Origuchi, Tomoki [1 ,3 ]
Sakamoto, Junya [1 ,3 ]
Okita, Minoru [1 ,3 ]
机构
[1] Nagasaki Univ, Dept Phys Therapy Sci, Grad Sch Biomed Sci, Sakamoto 1-7-1, Nagasaki 8528520, Japan
[2] Seirei Christopher Univ, Sch Rehabil Sci, Dept Phys Therapy, Shizuoka, Japan
[3] Nagasaki Univ, Inst Biomed Sci, Nagasaki, Japan
[4] Nagasaki Univ Hosp, Dept Rehabil, Nagasaki, Japan
[5] Nagasaki Mem Hosp, Dept Rehabil, Nagasaki, Japan
关键词
apoptosis; cleaved caspase-3; fibrosis; immobilization; macrophages; MOLECULAR-MECHANISMS; UBIQUITIN-PROTEASOME; CELL-DEATH; RECOVERY; ATROPHY;
D O I
10.1002/mus.27473
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Introduction/Aims Although 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. Methods Eight-week-old Wistar rats were divided into immobilization and control groups, and the soleus muscles were selected for analysis. Results The 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. Discussion Myonuclear apoptosis via the upregulation of cleaved caspase-3 might induce macrophage accumulation. These alterations are related to immobilization-induced muscle fibrosis.
引用
收藏
页码:341 / 349
页数:9
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