Abstract

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.

Highlights

  • Skeletal muscle injury is a common disorder, especially among athletes [1,2,3,4,5,6,7]

  • We found no appreciable differences in muscle weight and muscle fiber size between BTB and CNC homology 1 (Bach1)-deficient and WT mice, indicating that Bach1 is dispensable for the development and maturation of the skeletal muscle system under the normal conditions

  • We found that a critical function of Bach1 in muscle cells manifested after muscle injury, wherethe amount of Bach1 proteinremarkably increased, presumably facilitatingthe required function for efficient muscle regeneration

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Summary

Introduction

Skeletal muscle injury is a common disorder, especially among athletes [1,2,3,4,5,6,7]. It is critical to understand the regeneration process of skeletal muscle to solve injury-related problems. Recent studies have revealed a negative function of BTB and CNC homology 1 (Bach1)to exacerbate tissue damages in multiple disease models [9,10,11,12,13,14,15]. Bach1-deficient mice show less area of infarction after an ischemia-reperfusion model of the heart [9]. Bach is a transcription regulatory protein that is broadly expressed in diverse range of tissues in both mice and human [16, 17].

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