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

Suzuki, Katsushi; Matsumoto, Mitsuyo; Katoh, Yohei; Liu, Liang; Ochiai, Kyoko; Aizawa, Yuta; Nagatomi, Ryoichi; Okuno, Hiroshi; Itoi, Eiji; Igarashi, Kazuhiko

doi:10.1371/journal.pone.0236781

Cited by 14 publications

(9 citation statements)

References 59 publications

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“…Smad2 is an important effector of the TGF-β signaling cascade in response to TGF-βs stimulation (containing MSTN). MSTN interacts with receptors, which triggers Smad2 and Smad3 phosphorylation, subsequently forming a complex of the phosphorylated Smad2/3 and Smad4 in the nucleus to regulate skeletal muscle development. , Recent studies have also reported that activation of endogenous Smad2 can lead to muscle atrophy, whereas inhibition of Smad2 can promote myogenic differentiation. − Similarly, we found that Smad2 overexpression significantly inhibited the differentiation of C2C12 myoblasts, whereas knockdown of endogenous Smad2 promoted their differentiation. In addition, we also verified a Smad2 -mediated effect of miR-455-3p on differentiation by cotransfecting miR-455-3p mimics and Smad2 -overexpressing plasmids.…”

Section: Discussionsupporting

confidence: 59%

miR-455-3p Is Negatively Regulated by Myostatin in Skeletal Muscle and Promotes Myoblast Differentiation

Han

Gao

Chang

et al. 2022

J. Agric. Food Chem.

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Myostatin (MSTN) is a growth and differentiation factor that regulates proliferation and differentiation of myoblasts, which in turn controls skeletal muscle growth. It may regulate myoblast differentiation by influencing miRNA expression, and the present study aimed to clarify its precise mechanism of action. Here, we found that MSTN −/− pigs showed an overgrowth of skeletal muscle and upregulated miR-455-3p level. Intervention of MSTN expression using siMSTN in C2C12 myoblasts also showed that siMSTN significantly increased the expression of miR-455-3p. It was found that miR-455-3p directly targeted the 3′-untranslated region of Smad2 by dual-luciferase assay. qRT-PCR, Western blotting, and immunofluorescence analyses indicated that miR-455-3p overexpression or Smad2 silencing in C2C12 myoblasts significantly promoted myoblast differentiation. Furthermore, siMSTN significantly increased the expression of GATA3. The levels of miR-455-3p were considerably reduced in C2C12 myoblasts following GATA3 knockdown. Consistently, GATA3 knockdown also reduced the enhanced miR-455-3p expression caused by siMSTN. Finally, we illustrated that GATA3 has a role in myoblast differentiation regulation. Taken together, we identified the expression profiles of miRNAs in MSTN −/− pigs and found that miR-455-3p positively regulates myoblast differentiation. In addition, we revealed that MSTN acts through the GATA3/miR-455-3p/Smad2 cascade to regulate muscle development.

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Section: Discussionsupporting

confidence: 59%

miR-455-3p Is Negatively Regulated by Myostatin in Skeletal Muscle and Promotes Myoblast Differentiation

Han

Gao

Chang

et al. 2022

J. Agric. Food Chem.

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“…Most DNA target sites identified in the distal silencer (-1424/-2000) by the TFSEARCH analysis have been reported to bind TFs such as AREB6, ARP-1, Bach1 and Evi1 (Supplementary Table S2), which have been reported to function as transcriptional repressors [90][91][92][93][94][95]. Therefore, the repressive action of these TFs, once they have bound to their target sites in the CLU silencer, may, at least in part, contribute to the differential expression observed for the CLU gene in our hTEC model.…”

Section: Discussionmentioning

confidence: 99%

Contribution of the Transcription Factors Sp1/Sp3 and AP-1 to Clusterin Gene Expression during Corneal Wound Healing of Tissue-Engineered Human Corneas

Gross

Le‐Bel

Desjardins

et al. 2021

IJMS

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In order to reduce the need for donor corneas, understanding of corneal wound healing and development of an entirely tissue-engineered human cornea (hTECs) is of prime importance. In this study, we exploited the hTEC to determine how deep wound healing affects the transcriptional pattern of corneal epithelial cells through microarray analyses. We demonstrated that the gene encoding clusterin (CLU) has its expression dramatically repressed during closure of hTEC wounds. Western blot analyses confirmed a strong reduction in the expression of the clusterin isoforms after corneal damage and suggest that repression of CLU gene expression might be a prerequisite to hTEC wound closure. Transfection with segments from the human CLU gene promoter revealed the presence of three regulatory regions: a basal promoter and two more distal negative regulatory regions. The basal promoter bears DNA binding sites for very potent transcription factors (TFs): Activator Protein-1 (AP-1) and Specificity protein-1 and 3 (Sp1/Sp3). By exploiting electrophoretic mobility shift assays (EMSA), we demonstrated that AP-1 and Sp1/Sp3 have their DNA binding site overlapping with one another in the basal promoter of the CLU gene in hCECs. Interestingly, expression of both these TFs is reduced (at the protein level) during hTEC wound healing, thereby contributing to the extinction of CLU gene expression during that process. The results of this study contribute to a better understanding of the molecular mechanisms accounting for the repression of CLU gene expression during corneal wound healing.

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“…Myostatin is synthesized and secreted primarily by skeletal muscle cells and signals through the activin-type II receptor (ActRII) [ 18 ]. ActRII recruits an Alk family kinase, leading to the activation of the small mother against decapentaplegic (Smad) 2/3 transcription factor complex that mediates inhibition of genes associated with muscle differentiation [ 19 ]. A study by Conery and colleagues documented that activation of Akt downregulates ActRIIB, blocking the atrophy-inducing effects of the constitutively active activin receptor-like kinase (ALK) 4/5 [ 20 ].…”

Section: Cellular Processes Involved In Muscle Mass Homeostasismentioning

confidence: 99%

Cancer-Related Cachexia: The Vicious Circle between Inflammatory Cytokines, Skeletal Muscle, Lipid Metabolism and the Possible Role of Physical Training

Mangano

Fouani

D’Amico

et al. 2022

IJMS

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Cachexia is a multifactorial and multi-organ syndrome that is a major cause of morbidity and mortality in late-stage chronic diseases. The main clinical features of cancer-related cachexia are chronic inflammation, wasting of skeletal muscle and adipose tissue, insulin resistance, anorexia, and impaired myogenesis. A multimodal treatment has been suggested to approach the multifactorial genesis of cachexia. In this context, physical exercise has been found to have a general effect on maintaining homeostasis in a healthy life, involving multiple organs and their metabolism. The purpose of this review is to present the evidence for the relationship between inflammatory cytokines, skeletal muscle, and fat metabolism and the potential role of exercise training in breaking the vicious circle of this impaired tissue cross-talk. Due to the wide-ranging effects of exercise training, from the body to the behavior and cognition of the individual, it seems to be able to improve the quality of life in this syndrome. Therefore, studying the molecular effects of physical exercise could provide important information about the interactions between organs and the systemic mediators involved in the overall homeostasis of the body.

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

Cited by 14 publications

References 59 publications

miR-455-3p Is Negatively Regulated by Myostatin in Skeletal Muscle and Promotes Myoblast Differentiation

miR-455-3p Is Negatively Regulated by Myostatin in Skeletal Muscle and Promotes Myoblast Differentiation

Contribution of the Transcription Factors Sp1/Sp3 and AP-1 to Clusterin Gene Expression during Corneal Wound Healing of Tissue-Engineered Human Corneas

Cancer-Related Cachexia: The Vicious Circle between Inflammatory Cytokines, Skeletal Muscle, Lipid Metabolism and the Possible Role of Physical Training

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