Expression of connexins during differentiation and regeneration of skeletal muscle:: functional relevance of connexin43
Expression of connexins during differentiation and regeneration of skeletal muscle:: functional relevance of connexin43
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DOI：
10.1242/jcs.01553
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发表时间：
2005-01-01
影响因子：
4
通讯作者：
Sáez, JC
中科院分区：
文献类型：
--
作者：
Araya, R;Eckardt, D;Sáez, JC
调控骨骼肌再生和分化的分子机制还不是很清楚。我们分析了连接蛋白(CXS)40、43和45在正常和再生的胫前肌以及成年和新生小鼠成肌细胞原代培养中的表达。CXS-45和CXS-43在正常肌肉中有较强的表达，而CXS-40在正常肌肉中没有表达，并且在再生过程中表达上调。此外，在转基因小鼠中诱导Cx43缺失后，研究了Cx43在分化和再生过程中的功能作用。在体内，Cx43的可诱导缺失延迟了肌纤维的形成，并延长了再生过程中肌生成素的表达。在卫星细胞来源的成肌细胞的原代培养中，Cx43的诱导缺失导致肌生成素和MyoD的表达降低，染料偶联，肌酸激酶活性降低，成肌细胞融合。因此，Cx45和Cx43的表达在骨骼肌再生过程中上调，而Cx43是正常的体外肌肉发生和体内成年肌肉再生所必需的。
The molecular mechanisms regulating skeletal muscle regeneration and differentiation are not well understood. We analyzed the expression of connexins (Cxs) 40, 43 and 45 in normal and regenerating tibialis anterior muscle and in primary cultures of differentiating myoblasts in adult and newborn mice, respectively. Cxs 45 and 43, but not 40, were strongly expressed in normal muscle and their expression was upregulated during regeneration. Furthermore, the functional role of Cx43 during differentiation and regeneration was examined after induced deletion of Cx43 in transgenic mice. In vivo, the inducible deletion of Cx43 delayed the formation of myofibers and prolonged the expression of myogenin during regeneration. In primary cultures of satellite cell-derived myoblasts, induced deletion of Cx43 led to decreased expression of myogenin and MyoD, dye coupling, creatine kinase activity and myoblast fusion. Thus, the expression of Cx45 and Cx43 is upregulated during skeletal muscle regeneration and Cx43 is required for normal myogenesis in vitro and adult muscle regeneration in vivo.