Bach1 promotes muscle regeneration through repressing Smad-mediated inhibition of myoblast differentiation

• DOI: 10.1371/journal.pone.0236781
• Publication Date: 2020-08-10T17:42:08Z
• Authors: Katsushi Suzuki; Mitsuyo Matsumoto; Yasutake Katoh; Liang Liu; Kyoko Ochiai; Yuta Aizawa; Ryoichi Nagatomi; Hiroshi Okuno; Eiji Itoi; Kazuhiko Igarashi
• Keywords: 0301 basic medicine; Science; Q; R; Cell Differentiation; Smad Proteins; Cell Line; Myoblasts; Mice; 03 medical and health sciences; Basic-Leucine Zipper Transcription Factors; Gene Knockdown Techniques; Medicine; Animals; Regeneration; Gene Silencing; Muscle, Skeletal; Transcriptome; Research Article

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.