scholarly journals MicroRNA-24-3p promotes skeletal muscle differentiation and regeneration by regulating HMGA1

2021 ◽  
Author(s):  
Paromita Dey ◽  
Miles A Soyer ◽  
Bijan K Dey
Keyword(s):  
Skeletal Muscle ◽  
Tibialis Anterior Muscle ◽  
High Mobility ◽  
Muscle Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Myoblast Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Muscle Stem Cells ◽  
Downstream Target

Abstract Numerous studies have established the critical roles of microRNAs in regulating posttranscriptional gene expression in diverse biological processes. Here, we report on the role and mechanism of miR-24-3p in skeletal muscle differentiation and regeneration. miR-24-3p promotes myoblast differentiation and skeletal muscle regeneration by directly targeting high mobility group AT-hook 1 (HMGA1) and regulating it and its direct downstream target, the inhibitor of differentiation 3 (ID3). miR-24-3p knockdown in neonatal mice increases PAX7-positive proliferating muscle stem cells (MuSCs) by derepressing Hmga1 and Id3 . Similarly, inhibiting miR24-3p in the tibialis anterior muscle prevents Hmga1 and Id3 downregulation and impairs regeneration. These findings provide evidence that the miR-24-3p/HMGA1/ID3 axis is required for MuSC differentiation and regeneration in vivo .

scholarly journals MicroRNA-24-3p promotes skeletal muscle differentiation and regeneration by regulating high mobility group AT-hook 1

2020 ◽  
Author(s):  
Paromita Dey ◽  
Bijan K. Dey
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
High Mobility ◽  
Muscle Differentiation ◽  
High Mobility Group ◽  
Skeletal Muscle Regeneration ◽  
Myoblast Differentiation ◽  
Skeletal Muscle Differentiation

AbstractSkeletal muscle regenerates throughout the lifetime to maintain normal development, growth, and physiological function. Skeletal muscle regeneration occurs in a coordinated fashion and requires strict regulation of myogenic gene expression during the process. Numerous studies have established the critical role of microRNAs in regulating post-transcriptional gene expression in diverse biological processes including differentiation, development, and regeneration. We have revealed in an earlier study that a large number of microRNAs were differentially expressed during myoblast differentiation. Here, we report the role of one such microRNA, the miR-24-3p, in skeletal muscle differentiation and regeneration. miR-24-3p is induced during myoblast differentiation and skeletal muscle regeneration. Exogenous miR-24-3p promotes while inhibition of miR-24-3p represses myoblast differentiation. miR-24-3p promotes myoblast differentiation by directly targeting and regulating the high mobility group AT-hook 1 (HMGA1). Consistent with the finding that HMGA1 is a repressor of myogenic differentiation, the miR-24-3p-resistant form of HMGA1 devoid of 3’untranslated region, inhibits myoblast differentiation. Intramuscular injection of antagomirs specific to miR-24-3p into the tibialis anterior muscle prevents HMGA1 down-regulation and impairs regeneration. These findings provide evidence for the requirement of the miR-24-3p/HMGA1 axis for skeletal muscle differentiation and regeneration.

scholarly journals Conditional Deletion of Dicer in Adult Mice Impairs Skeletal Muscle Regeneration

2019 ◽  
Vol 20 (22) ◽  
pp. 5686 ◽  
Author(s):  
Satoshi Oikawa ◽  
Minjung Lee ◽  
Takayuki Akimoto
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Tibialis Anterior Muscle ◽  
Critical Factor ◽  
Skeletal Muscle Regeneration ◽  
Small Noncoding Rnas ◽  
Adult Mice

Skeletal muscle has a remarkable regenerative capacity, which is orchestrated by multiple processes, including the proliferation, fusion, and differentiation of the resident stem cells in muscle. MicroRNAs (miRNAs) are small noncoding RNAs that mediate the translational repression or degradation of mRNA to regulate diverse biological functions. Previous studies have suggested that several miRNAs play important roles in myoblast proliferation and differentiation in vitro. However, their potential roles in skeletal muscle regeneration in vivo have not been fully established. In this study, we generated a mouse in which the Dicer gene, which encodes an enzyme essential in miRNA processing, was knocked out in a tamoxifen-inducible way (iDicer KO mouse) and determined its regenerative potential after cardiotoxin-induced acute muscle injury. Dicer mRNA expression was significantly reduced in the tibialis anterior muscle of the iDicer KO mice, whereas the expression of muscle-enriched miRNAs was only slightly reduced in the Dicer-deficient muscles. After cardiotoxin injection, the iDicer KO mice showed impaired muscle regeneration. We also demonstrated that the number of PAX7+ cells, cell proliferation, and the myogenic differentiation capacity of the primary myoblasts did not differ between the wild-type and the iDicer KO mice. Taken together, these data demonstrate that Dicer is a critical factor for muscle regeneration in vivo.

scholarly journals Zfp422 promotes skeletal muscle differentiation by regulating EphA7 to induce appropriate myoblast apoptosis

2019 ◽  
Vol 27 (5) ◽  
pp. 1644-1659 ◽  
Author(s):  
Yaping Nie ◽  
Shufang Cai ◽  
Renqiang Yuan ◽  
Suying Ding ◽  
Xumeng Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Zinc Finger ◽  
Muscle Development ◽  
Zinc Finger Protein ◽  
Critical Role ◽  
Muscle Differentiation ◽  
C2c12 Cells ◽  
Myoblast Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Finger Protein

Abstract Zinc finger protein 422 (Zfp422) is a widely expressed zinc finger protein that serves as a transcriptional factor to regulate downstream gene expression, but until now, little is known about its roles in myogenesis. We found here that Zfp422 plays a critical role in skeletal muscle development and regeneration. It highly expresses in mouse skeletal muscle during embryonic development. Specific knockout of Zfp422 in skeletal muscle impaired embryonic muscle formation. Satellite cell-specific Zfp422 deletion severely inhibited muscle regeneration. Myoblast differentiation and myotube formation were suppressed in Zfp422-deleted C2C12 cells, isolated primary myoblasts, and satellite cells. Chromatin Immunoprecipitation Sequencing (ChIP-Seq) revealed that Zfp422 regulated ephrin type-A receptor 7 (EphA7) expression by binding an upstream 169-bp DNA sequence, which was proved to be an enhancer of EphA7. Knocking EphA7 down in C2C12 cells or deleting Zfp422 in myoblasts will inhibit cell apoptosis which is required for myoblast differentiation. These results indicate that Zfp422 is essential for skeletal muscle differentiation and fusion, through regulating EphA7 expression to maintain proper apoptosis.

scholarly journals Enhanced expression of mouse c-ski accompanies terminal skeletal muscle differentiation in vivo and in vitro

1995 ◽  
Vol 204 (3) ◽  
pp. 291-300 ◽  
Author(s):  
Stephanie Namciu ◽  
Gary E. Lyons ◽  
Bruce K. Micales ◽  
Hong-Chen Heyman ◽  
Clemencia Colmenares ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Enhanced Expression

scholarly journals Klf5 regulates muscle differentiation by directly targeting muscle-specific genes in cooperation with MyoD in mice

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Shinichiro Hayashi ◽  
Ichiro Manabe ◽  
Yumi Suzuki ◽  
Frédéric Relaix ◽  
Yumiko Oishi
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Muscle Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Biological Processes ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Acting In Concert

Krüppel-like factor 5 (Klf5) is a zinc-finger transcription factor that controls various biological processes, including cell proliferation and differentiation. We show that Klf5 is also an essential mediator of skeletal muscle regeneration and myogenic differentiation. During muscle regeneration after injury (cardiotoxin injection), Klf5 was induced in the nuclei of differentiating myoblasts and newly formed myofibers expressing myogenin in vivo. Satellite cell-specific Klf5 deletion severely impaired muscle regeneration, and myotube formation was suppressed in Klf5-deleted cultured C2C12 myoblasts and satellite cells. Klf5 knockdown suppressed induction of muscle differentiation-related genes, including myogenin. Klf5 ChIP-seq revealed that Klf5 binding overlaps that of MyoD and Mef2, and Klf5 physically associates with both MyoD and Mef2. In addition, MyoD recruitment was greatly reduced in the absence of Klf5. These results indicate that Klf5 is an essential regulator of skeletal muscle differentiation, acting in concert with myogenic transcription factors such as MyoD and Mef2.

scholarly journals MyoD-positive epiblast cells regulate skeletal muscle differentiation in the embryo

2006 ◽  
Vol 175 (2) ◽  
pp. 283-292 ◽  
Author(s):  
Jacquelyn Gerhart ◽  
Justin Elder ◽  
Christine Neely ◽  
Jared Schure ◽  
Tage Kvist ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Body Wall ◽  
Muscle Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Muscle Stem Cells ◽  
Skeletal Muscle Stem Cells

MyoD mRNA is expressed in a subpopulation of cells within the embryonic epiblast. Most of these cells are incorporated into somites and synthesize Noggin. Ablation of MyoD-positive cells in the epiblast subsequently results in the herniation of organs through the ventral body wall, a decrease in the expression of Noggin, MyoD, Myf5, and myosin in the somites and limbs, and an increase in Pax-3–positive myogenic precursors. The addition of Noggin lateral to the somites compensates for the loss of MyoD-positive epiblast cells. Skeletal muscle stem cells that arise in the epiblast are utilized in the somites to promote muscle differentiation by serving as a source of Noggin.

scholarly journals Aurora kinase A mediated phosphorylation of mPOU is critical for skeletal muscle differentiation

2019 ◽  
Author(s):  
Dhanasekaran Karthigeyan ◽  
Arnab Bose ◽  
Ramachandran Boopathi ◽  
Vinay Jaya Rao ◽  
Hiroki Shima ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Aurora Kinase ◽  
Muscle Differentiation ◽  
Negative Regulator ◽  
Myoblast Differentiation ◽  
C2c12 Myoblast ◽  
Skeletal Muscle Differentiation ◽  
Skeletal Myogenesis ◽  
Aurora Kinase A ◽  
Kinase A

AbstractAurora kinases are Ser/Thr-directed protein kinases which play pivotal roles in mitosis. Recent evidences highlight the importance of these kinases in non-mitotic biological events like skeletal myogenesis. Our earlier study identified POU6F1 (or mPOU) as a novel Aurora kinase A (AurkA) substrate. Here, we report that AurkA phosphorylates POU6F1 at Ser197 and inhibits its DNA binding ability. Delving into POU6F1 physiology, we find that the phospho-mimic (S197D) POU6F1 mutant exhibits enhancement, while wild type (WT) or phospho-deficient (S197A) mutant shows retardation in C2C12 myoblast differentiation. Interestingly, POU6F1 depletion phenocopies S197D-POU6F1 overexpression in the differentiation context. Collectively, our results signify mPOU as a negative regulator of skeletal muscle differentiation and strengthens the importance of AurkA in skeletal myogenesis.

scholarly journals 6-Bromoindirubin-3′-oxime intercepts GSK3 signaling to promote and enhance skeletal muscle differentiation affecting miR-206 expression in mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Elvira Ragozzino ◽  
Mariarita Brancaccio ◽  
Antonella Di Costanzo ◽  
Francesco Scalabrì ◽  
Gennaro Andolfi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Myogenic Differentiation ◽  
Muscle Differentiation ◽  
C2c12 Cells ◽  
Skeletal Muscle Differentiation ◽  
Myoblast Proliferation ◽  
Enhanced Expression ◽  
Pharmacologically Active

AbstractDystrophies are characterized by progressive skeletal muscle degeneration and weakness as consequence of their molecular abnormalities. Thus, new drugs for restoring skeletal muscle deterioration are critically needed. To identify new and alternative compounds with a functional role in skeletal muscle myogenesis, we screened a library of pharmacologically active compounds and selected the small molecule 6-bromoindirubin-3′-oxime (BIO) as an inhibitor of myoblast proliferation. Using C2C12 cells, we examined BIO’s effect during myoblast proliferation and differentiation showing that BIO treatment promotes transition from cell proliferation to myogenic differentiation through the arrest of cell cycle. Here, we show that BIO is able to promote myogenic differentiation in damaged myotubes in-vitro by enriching the population of newly formed skeletal muscle myotubes. Moreover, in-vivo experiments in CTX-damaged TA muscle confirmed the pro-differentiation capability of BIO as shown by the increasing of the percentage of myofibers with centralized nuclei as well as by the increasing of myofibers number. Additionally, we have identified a strong correlation of miR-206 with BIO treatment both in-vitro and in-vivo: the enhanced expression of miR-206 was observed in-vitro in BIO-treated proliferating myoblasts, miR-206 restored expression was observed in a forced miR-206 silencing conditions antagomiR-mediated upon BIO treatment, and in-vivo in CTX-injured muscles miR-206 enhanced expression was observed upon BIO treatment. Taken together, our results highlight the capacity of BIO to act as a positive modulator of skeletal muscle differentiation in-vitro and in-vivo opening up a new perspective for novel therapeutic targets to correct skeletal muscle defects.

scholarly journals Zeb2 Regulates Myogenic Differentiation in Pluripotent Stem Cells

2020 ◽  
Vol 21 (7) ◽  
pp. 2525
Author(s):  
Ester Sara Di Filippo ◽  
Domiziana Costamagna ◽  
Giorgia Giacomazzi ◽  
Álvaro Cortés-Calabuig ◽  
Agata Stryjewska ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Transcription Factors ◽  
Zinc Finger ◽  
Pluripotent Stem Cells ◽  
Myogenic Differentiation ◽  
Muscle Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Skeletal Muscle Differentiation ◽  
E Box

Skeletal muscle differentiation is triggered by a unique family of myogenic basic helix-loop-helix transcription factors, including MyoD, MRF-4, Myf-5, and Myogenin. These transcription factors bind promoters and distant regulatory regions, including E-box elements, of genes whose expression is restricted to muscle cells. Other E-box binding zinc finger proteins target the same DNA response elements, however, their function in muscle development and regeneration is still unknown. Here, we show that the transcription factor zinc finger E-box-binding homeobox 2 (Zeb2, Sip-1, Zfhx1b) is present in skeletal muscle tissues. We investigate the role of Zeb2 in skeletal muscle differentiation using genetic tools and transgenic mouse embryonic stem cells, together with single-cell RNA-sequencing and in vivo muscle engraftment capability. We show that Zeb2 over-expression has a positive impact on skeletal muscle differentiation in pluripotent stem cells and adult myogenic progenitors. We therefore propose that Zeb2 is a novel myogenic regulator and a possible target for improving skeletal muscle regeneration. The non-neural roles of Zeb2 are poorly understood.

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