β-Catenin Activation in Muscle Progenitor Cells Regulates Tissue Repair

Rudolf, Anja; Schirwis, Elija; Giordani, Lorenzo; Parisi, Alice; Lepper, Christoph; Taketo, Makoto Mark; Grand, Fabien Le

doi:10.1016/j.celrep.2016.04.022

Cited by 93 publications

(125 citation statements)

References 33 publications

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“…Our experiments further show that endogenous Axin2 expression is absent in myoblasts (Fig. 1A,B,D), which is in accordance with recent data demonstrating that only very low levels of active β-catenin protein are found in undifferentiated muscle progenitors (Rudolf et al, 2016). We therefore speculate that canonical Wnt signaling is an important player in the differentiation process (from myoblasts to myotubes) but is not required for satellite cell maintenance.…”

Section: Discussionsupporting

confidence: 78%

“…This is in line with several publications showing that activated β-catenin modulates myogenic differentiation (Gavard et al, 2004;Goichberg et al, 2001;Martin et al, 2002;Rudolf et al, 2016).…”

Section: Canonical Wnts Regulate the Influence Of β-Catenin/tcf/lef Asupporting

confidence: 79%

“…9E-G), further supporting the notion of delayed differentiation upon strong activation of Wnt/β-catenin signaling. Recent studies employing genetic non-degradable β-catenin mutants in satellite cell progeny reported controversial results concerning the muscle regeneration phenotype in loss-versus gain-of-function mutants, but both underline the necessity for strict regulation of β-catenin signaling activity during muscle regeneration (Murphy et al, 2014;Rudolf et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

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Wnt/β-catenin signaling via Axin2 is required for myogenesis and, together with YAP/Taz and Tead1, active in IIa/IIx muscle fibers

et al. 2016

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Canonical Wnt/β-catenin signaling plays an important role in myogenic differentiation, but its physiological role in muscle fibers remains elusive. Here, we studied activation of Wnt/β-catenin signaling in adult muscle fibers and muscle stem cells in an Axin2 reporter mouse. Axin2 is a negative regulator and a target of Wnt/β-catenin signaling. In adult muscle fibers, Wnt/β-catenin signaling is only detectable in a subset of fast fibers that have a significantly smaller diameter than other fast fibers. In the same fibers, immunofluorescence staining for YAP/Taz and Tead1 was detected. Wnt/β-catenin signaling was absent in quiescent and activated satellite cells. Upon injury, Wnt/β-catenin signaling was detected in muscle fibers with centrally located nuclei. During differentiation of myoblasts expression of Axin2, but not of Axin1, increased together with Tead1 target gene expression. Furthermore, absence of Axin1 and Axin2 interfered with myoblast proliferation and myotube formation, respectively. Treatment with the canonical Wnt3a ligand also inhibited myotube formation. Wnt3a activated TOPflash and Tead1 reporter activity, whereas neither reporter was activated in the presence of Dkk1, an inhibitor of canonical Wnt signaling. We propose that Axin2-dependent Wnt/β-catenin signaling is involved in myotube formation and, together with YAP/Taz/Tead1, associated with reduced muscle fiber diameter of a subset of fast fibers.

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Section: Discussionsupporting

confidence: 78%

Section: Canonical Wnts Regulate the Influence Of β-Catenin/tcf/lef Asupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

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Wnt/β-catenin signaling via Axin2 is required for myogenesis and, together with YAP/Taz and Tead1, active in IIa/IIx muscle fibers

et al. 2016

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“…We then investigated if Wnt/β-catenin target genes expressions could be induced in Rspo1 - null cells following exogenous ligand stimulation. Following WNT3A protein treatment, control myocytes exhibited elevated expression of the β-catenin responsive genes Fst , Gja5 , and Tgfb2 (Figures 3I, 3K, and 3M) (Rudolf et al., 2016). In contrast, Rspo1 - null myocytes did not respond to exogenous WNT3A stimulation (Figures 3J, 3L, and 3N).…”

Section: Resultsmentioning

confidence: 98%

R-spondin1 Controls Muscle Cell Fusion through Dual Regulation of Antagonistic Wnt Signaling Pathways

F¹,

Vezin²,

Bentzinger³

et al. 2017

Cell Reports

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SummaryWnt-mediated signals are involved in many important steps in mammalian regeneration. In multiple cell types, the R-spondin (Rspo) family of secreted proteins potently activates the canonical Wnt/β-catenin pathway. Here, we identify Rspo1 as a mediator of skeletal muscle tissue repair. First, we show that deletion of Rspo1 results in global alteration of muscle regeneration kinetics following acute injury. We find that muscle progenitor cells lacking Rspo1 show delayed differentiation due to reduced activation of Wnt/β-catenin target genes. Furthermore, muscle cells lacking Rspo1 have a fusion phenotype leading to larger myotubes containing supernumerary nuclei both in vitro and in vivo. The increase in muscle fusion was dependent on downregulation of Wnt/β-catenin and upregulation of non-canonical Wnt7a/Fzd7/Rac1 signaling. We conclude that reciprocal control of antagonistic Wnt signaling pathways by Rspo1 in muscle stem cell progeny is a key step ensuring normal tissue architecture restoration following acute damage.

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“…However, the role of S100A4 in cardiac fibrosis remains unknown. Wnt/β-catenin signaling pathway is connected with fibroblast activation [14] and tissue repair [15], including β-Catenin that activates gene transcription [16] and autocrine Wnt ligand production [17]. Stabilized β-catenin activates target genes, like S100A4, a process which leads to aggressive tumor growth, poor prognosis and serious metastasis [18].…”

Section: Introductionmentioning

confidence: 99%

Downregulation of S100A4 Alleviates Cardiac Fibrosis via Wnt/β -Catenin Pathway in Mice

Hong

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cardiac fibrosis is a pathological change leading to cardiac remodeling during the progression of myocardial ischemic diseases, and its therapeutic strategy remains to be explored. S100A4, a calcium-binding protein, participates in fibrotic diseases with an unclear mechanism. This study aimed to investigate the role of S100A4 in cardiac fibrosis. Methods: Cardiac fibroblasts from neonatal C57BL/6 mouse hearts were isolated and cultured. Myocardial infarction was induced by ligating the left anterior descending coronary artery (LAD). The ligation was not performed in the sham group. A volume of 5×10⁵pfu/g adenovirus or 5 µM/g ICG-001 was intramyocardially injected into five parts bordering the infarction zone or normal region. We used Western blotting, quantitative RT-PCR, immunofluorescence, immunohistochemistry and Masson’s trichrome staining to explore the function of S100A4. Results: We found significant increases of S100A4 level and cardiac fibrosis markers, and β-catenin signaling activation in vitro and in vivo. In addition, knockdown of S100A4 significantly reduced cardiac fibrosis and β-catenin levels. Moreover, the expression of S100A4 decreased after ICG-001 inhibited β-catenin signal pathway. Conclusion: Downregulation of S100A4 alleviates cardiac fibrosis via Wnt/β -catenin pathway in mice. S100A4 may be a therapeutic target of cardiac fibrosis.

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β-Catenin Activation in Muscle Progenitor Cells Regulates Tissue Repair

Cited by 93 publications

References 33 publications

Wnt/β-catenin signaling via Axin2 is required for myogenesis and, together with YAP/Taz and Tead1, active in IIa/IIx muscle fibers

Wnt/β-catenin signaling via Axin2 is required for myogenesis and, together with YAP/Taz and Tead1, active in IIa/IIx muscle fibers

R-spondin1 Controls Muscle Cell Fusion through Dual Regulation of Antagonistic Wnt Signaling Pathways

Downregulation of S100A4 Alleviates Cardiac Fibrosis via Wnt/β -Catenin Pathway in Mice

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