Midkine-deficient mice delayed degeneration and regeneration after skeletal muscle injury

Midkine-deficient mice delayed degeneration and regeneration after skeletal muscle injury
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DOI:
10.1016/j.acthis.2013.08.009
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发表时间:
2014-01-01
期刊:
影响因子:
2.5
通讯作者:
Yoshida, Yoshihiro
Yoshida, Yoshihiro
中科院分区:
生物学4区
文献类型:
--
作者:
Ikutomo, Masako;Sakakima, Harutoshi;Yoshida, Yoshihiro

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中期因子(MK),肝素结合生长因子,以前被发现在大鼠肌管形成阶段表达。我们研究了MK基因缺陷(Mdk(-/-))小鼠在布比卡因注射到胫骨前肌损伤后骨骼肌变性和再生。损伤肌肉可见强烈的炎性细胞浸润。损伤后7天,Mdk(-/-)小鼠的肌管(细胞质中具有位于中央的细胞核的肌纤维)显著小于野生型(Mdk(+/+))小鼠(p = 0.02)。肌管大小的分布在5和7天两组之间显示出定量差异,但在14天没有。Mdk(-/1-)小鼠伤后5、7天再生区出现大量细小肌管,而Mdk(+/+)小鼠伤后5、7天再生区出现大量细小肌管。损伤后3天,Mdk(-/-)小鼠中巨噬细胞标志物Iba 1的表达显著降低(p = 0.01)。Mdk(-/-)组成肌细胞等结蛋白阳性细胞数明显少于Mdleif组。我们的研究结果表明,MK的缺失导致再生延迟,之前的巨噬细胞迁移到受损区域的速度减慢,并且MK在骨骼肌损伤后的细胞分化和成熟中起作用。(c)2013 Elsevier GmbH. All rights reserved.
Midkine (MK), a heparin-binding growth factor, was previously found to be expressed in the rat myotubeforming stage. We investigated MK gene-deficient (Mdk(-/-)) mice in terms of skeletal muscle degeneration and regeneration after injury by bupivacaine injection into the tibialis anterior muscle. Injured muscles showed intense inflammatory cell infiltration. Myotubes, myofibers with centrally located nuclei in their cytoplasm, were significantly smaller in Mdk(-/-) mice than in wild type (Mdk(+/+)) mice 7 days after injury (p = 0.02). The distribution of myotube sizes showed quantitative differences between the two groups at 5 and 7 days, but not at 14 days. Many small myotubes were found in the regenerative area of Mdk(-/1-) mice compared with that of Mdk(+/+)mice 5 and 7 days after injury. The expression of Iba1, a macrophage marker, was significantly lower in Mdk(-/-) mice 3 days after injury (p = 0.01). The number of desminpositive cells like myoblasts in Mdk(-/-) mice was significantly fewer than that in Mdleif mice 3 days after injury. Our results suggested that deletion of MK results in a delay in regeneration, preceded by decelerated migration of macrophages to the damaged area, and that MK has a role in cell differentiation and maturation after skeletal muscle injury. (c) 2013 Elsevier GmbH. All rights reserved.