Regulation of the Follistatin Gene by RSPO-LGR4 Signaling via Activation of the WNT/β-Catenin Pathway in Skeletal Myogenesis

Han, Xiuzhen; Jin, Yong-Ri; Tan, Leonard; Kosciuk, Tatiana; Lee, Jinseon; Yoon, Jong‐Hwan

doi:10.1128/mcb.01285-13

Cited by 44 publications

(34 citation statements)

References 56 publications

(86 reference statements)

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“…Follistatin is a functional antagonist of the TGF‐ β family that inhibits MSTN and induces skeletal hypertrophy . Moreover, follistatin has been used in gene therapy for myopathies due to its effects on the MSTN pathway .…”

Section: Discussionmentioning

confidence: 99%

“…Follistatin is a functional antagonist of the TGF-family that inhibits MSTN and induces skeletal hypertrophy. [21][22][23] Moreover, follistatin has been used in gene therapy for myopathies due to its effects on the MSTN pathway. 24 Another study demonstrated that follistatin is essential for skeletal muscle hypertrophy independently of MSTN.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of internal organs between myostatin mutant and wild‐type piglets

Luo

Xuan

et al. 2019

J Sci Food Agric

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BACKGROUND Myostatin (MSTN) negatively regulates skeletal muscle development; however, its functions in internal organs have not been thoroughly investigated. Here, we compared the morphological, molecular, and biological characteristics of the heart, liver, spleen, lungs, kidneys, and tongue of homozygous MSTN mutant (MSTN−/−), heterozygous MSTN mutant (MSTN+/−), and wild‐type (WT) piglets. RESULTS The heart and liver were lighter in MSTN−/− piglets than in MSTN+/− piglets, while the tongue was heavier in MSTN−/− piglets than in WT piglets (P < 0.05). Furthermore, the tongue was longer in MSTN−/− piglets than in WT piglets, and myofibers of the tongue were significantly larger in the former piglets than in the latter ones (P < 0.01). mRNA expression of MSTN in all organs was significantly lower in MSTN−/− and MSTN+/− piglets than in WT piglets (P < 0.05). Meanwhile, mRNA expression of follistatin, which is closely related to MSTN, in the heart and liver was significantly higher in MSTN−/− piglets than in MSTN+/− and WT piglets (P < 0.05). In addition, protein expression of MSTN in the heart, kidneys, and tongue was significantly lower in MSTN−/− piglets than in WT piglets (P < 0.01). CONCLUSION These results suggest that MSTN is widely expressed and has marked effects in multiple internal organs. Myostatin has crucial functions in regulating internal organ size, especially the tongue. © 2019 Society of Chemical Industry

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparison of internal organs between myostatin mutant and wild‐type piglets

Luo

Xuan

et al. 2019

J Sci Food Agric

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“…INHBA , KIT , TGFB1 , and TGFB3 were upregulated while NT5E and FST were downregulated significantly in Jagged1‐treated hPDLs. Previous report suggested the strong possibility of cross‐talking between the WNT/β‐catenin and TGF‐β signaling pathways mediated by FST during myogenic differentiation (Han et al, ). NT5E is also known as CD73 .…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling of Jagged1‐treated human periodontal ligament cells

et al. 2019

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Objective: Jagged1 regulates several biological functions in human periodontal ligament cells (hPDLs). The present study aimed to evaluate mRNA expression profiling of Jagged1-treated hPDLs using microarray technique. Methods:Notch ligands, Jagged1, were indirectly immobilized on tissue culture surface. Subsequently, hPDLs were seeded on Jagged1 immobilized surface and maintained in growth medium for 48 hr. Total RNA was collected and processed. Gene expression profiling was examined using microarray technique. Real-time polymerase chain reaction and immunofluorescence staining were employed to determine mRNA and protein expression levels, respectively. Cell proliferation and colony-forming unit assay were performed. Cell cycle was evaluated using propidium iodide staining and flow cytometry analysis. Results:The isolated cells demonstrated fibroblast-like morphology and exhibited the co-expression of CD44, CD90, and CD105 surface markers. After stimulated with Jagged1, the total of 411 genes was differentially expressed, consisting both coding and non-coding genes. For coding genes, 165 and 160 coding genes were upregulated and downregulated, respectively. Pathway analysis revealed that the upregulated genes were mainly involved in cellular interactions, signal transduction, and collagen formation and degradation while the downregulated genes were in the events and phases in cell cycle. Jagged1 significantly decreased cell proliferation, reduced colony-forming unit ability, and induced G0/G1 cell cycle arrest in hPDLs.

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“…RSPO2 promotes myogenic differentiation and myocyte fusion via activation of WNT/␤-catenin signaling in C2C12 cells (55). RSPOs can regulate WNT receptor expression and control myogenesis through gene expression of the transforming growth factor ␤ (TGF␤) antagonist Fst (56). Thus, WNT signaling is activated through WNT ligands, RSPO, and noncanonical (␤-catenin-independent) WNT signaling activators during muscle development.…”

Section: Discussionmentioning

confidence: 99%

WNT/β-Catenin Signaling Regulates Multiple Steps of Myogenesis by Regulating Step-Specific Targets

Suzuki

Pelikan

Iwata

2015

Molecular and Cellular Biology

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cMolecules involved in WNT/␤-catenin signaling show specific spatiotemporal expression and play vital roles in myogenesis; however, it is still largely unknown how WNT/␤-catenin signaling regulates each step of myogenesis. Here, we show that WNT/ ␤-catenin signaling can control diverse biological processes of myogenesis by regulating step-specific molecules. In order to identify the temporally specific roles of WNT/␤-catenin signaling molecules in muscle development and homeostasis, we used in vitro culture systems for both primary mouse myoblasts and C2C12 cells, which can differentiate into myofibers. We found that a blockade of WNT/␤-catenin signaling in the proliferating cells decreases proliferation activity, but does not induce cell death, through the regulation of genes cyclin A2 (Ccna2) and cell division cycle 25C (Cdc25c). During muscle differentiation, the inhibition of WNT/␤-catenin signaling blocks myoblast fusion through the inhibition of the Fermitin family homolog 2 (Fermt2) gene. Blocking WNT/␤-catenin signaling in the well-differentiated myofibers results in the failure of maintenance of their structure by disruption of cadherin/␤-catenin/actin complex formation, which plays a crucial role in connecting a myofiber's cytoskeleton to the surrounding extracellular matrix. Thus, our results indicate that WNT/␤-catenin signaling can regulate multiple steps of myogenesis, including cell proliferation, myoblast fusion, and homeostasis, by targeting step-specific molecules.S keletal muscle plays highly specialized roles in the generation of force and is capable of extensive metabolic and functional plasticity. Skeletal muscle also exhibits robust regenerative capacity, and its formation is composed of complex and highly regulated processes among embryonic development and regeneration in mature skeletal musculature (1). Muscle precursor cells (also known as satellite cells in the adult) lie under, or are embedded in, the basal lamina of the myofiber in skeletal muscles and are the major source of regeneration and growth of skeletal muscles (2). During development and regeneration in response to injury or recovery from atrophy, muscle precursor cells start to proliferate, at which stage they are referred to as myoblasts, and subsequently differentiate to form new myofibers or fuse with existing myofibers (2). These processes require fine-tuned regulations of proliferation and differentiation that are likely regulated by signal transduction pathways.The WNT family (wingless-type mouse mammary tumor virus [MMTV] integration site family) of signaling molecules consists of 21 secreted glycoprotein ligands. WNT ligands are essential to activate downstream pathways (canonical ␤-catenin-dependent and/or noncanonical ␤-catenin-independent pathways) in physiological and pathological conditions. WNT/␤-catenin signaling can regulate a variety of genes in a specific spatiotemporal manner (3). In the absence of WNT ligands, ␤-catenin is incorporated into a protein complex containing axin, adenomatous polyposis coli (A...

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Regulation of the Follistatin Gene by RSPO-LGR4 Signaling via Activation of the WNT/β-Catenin Pathway in Skeletal Myogenesis

Cited by 44 publications

References 56 publications

Comparison of internal organs between myostatin mutant and wild‐type piglets

Comparison of internal organs between myostatin mutant and wild‐type piglets

Gene expression profiling of Jagged1‐treated human periodontal ligament cells

WNT/β-Catenin Signaling Regulates Multiple Steps of Myogenesis by Regulating Step-Specific Targets

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