Bach1 promotes muscle regeneration through repressing Smad-mediated inhibition of myoblast differentiation
Bach1 promotes muscle regeneration through repressing Smad-mediated inhibition of myoblast differentiation
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DOI：
10.1371/journal.pone.0236781
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发表时间：
2020-08
期刊：
影响因子：
3.7
通讯作者：
Katsushi Suzuki;Mitsuyo Matsumoto;Y. Katoh;Liang Liu;Kyoko Ochiai;Yuta Aizawa;R. Nagatomi;H. Okuno;E. Itoi;K. Igarashi
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文献类型：
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作者：
Katsushi Suzuki;Mitsuyo Matsumoto;Y. Katoh;Liang Liu;Kyoko Ochiai;Yuta Aizawa;R. Nagatomi;H. Okuno;E. Itoi;K. Igarashi
据报道，由于具有抗氧化功能的血红素加氧酶-1（HO-1）表达增加，Bach 1缺陷小鼠在不同疾病模型中表现出组织损伤减少。相反，我们发现小鼠Bach 1缺乏加重了心脏毒素引起的骨骼肌损伤。与对照细胞相比，使用RNA干扰抑制C2 C12成肌细胞中的Bach 1表达导致增殖、肌管形成和肌细胞生成素表达减少。虽然在C2 C12细胞中通过Bach 1沉默增加HO-1的表达，但是通过HO-1抑制不能挽救减少的肌管形成。在Bach 1缺陷小鼠和Bach 1沉默的C2 C12细胞中观察到Smad 2，Smad 3和FoxO 1（已知的肌细胞分化抑制剂）的上调。因此，Bach 1可能通过促进成肌细胞的增殖和分化来促进肌肉再生。
It has been reported that Bach1-deficient mice show reduced tissue injuries in diverse disease models due to increased expression of heme oxygenase-1 (HO-1)that possesses an antioxidant function. In contrast, we found that Bach1 deficiency in mice exacerbated skeletal muscle injury induced by cardiotoxin. Inhibition of Bach1 expression in C2C12 myoblast cells using RNA interference resulted in reduced proliferation, myotube formation, and myogenin expression compared with control cells. While the expression of HO-1 was increased by Bach1 silencing in C2C12 cells, the reduced myotube formation was not rescued by HO-1 inhibition. Up-regulations of Smad2, Smad3 and FoxO1, known inhibitors of muscle cell differentiation, were observed in Bach1-deficient mice and Bach1-silenced C2C12 cells. Therefore, Bach1 may promote regeneration of muscle by increasing proliferation and differentiation of myoblasts.