scholarly journals PC4/Tis7/IFRD1Stimulates Skeletal Muscle Regeneration and Is Involved in Myoblast Differentiation as a Regulator of MyoD and NF-κB

2010 ◽  
Vol 286 (7) ◽  
pp. 5691-5707 ◽  
Author(s):  
Laura Micheli ◽  
Luca Leonardi ◽  
Filippo Conti ◽  
Giovanna Maresca ◽  
Sandra Colazingari ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration ◽  
Myoblast Differentiation

scholarly journals Kinin-B2 Receptor Activity in Skeletal Muscle Regeneration and Myoblast Differentiation

2018 ◽  
Vol 15 (1) ◽  
pp. 48-58 ◽  
Author(s):  
Janaina M. Alves ◽  
Antonio H. Martins ◽  
Claudiana Lameu ◽  
Talita Glaser ◽  
Nawal M. Boukli ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Receptor Activity ◽  
Skeletal Muscle Regeneration ◽  
Myoblast Differentiation

scholarly journals ARHGEF3 regulates skeletal muscle regeneration and strength through autophagy

2020 ◽  
Author(s):  
Jae-Sung You ◽  
Nilmani Singh ◽  
Adriana Reyes-Ordonez ◽  
Nidhi Khanna ◽  
Zehua Bao ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Mammalian Target Of Rapamycin ◽  
Akt Signaling ◽  
Skeletal Muscle Regeneration ◽  
Myoblast Differentiation ◽  
Independent Manner ◽  
And Function ◽  
Old Mice

SummarySkeletal muscle regeneration is essential for restoring muscle function upon injury and for the maintenance of muscle health with aging. ARHGEF3, a Rho-specific GEF, negatively regulates myoblast differentiation via mammalian target of rapamycin complex 2 (mTORC2)-Akt signaling in a GEF-independent manner in vitro. Here, we investigated ARHGEF3’s role in skeletal muscle regeneration by creating ARHGEF3 KO mice. These mice exhibited no discernible phenotype under normal conditions. Upon injury, however, ARHGEF3 deficiency enhanced the mass, fiber size and function of regenerating muscles in both young and aged mice. Surprisingly, these effects were not mediated by mTORC2-Akt signaling, but by the GEF activity of ARHGEF3. Furthermore, ARHGEF3 KO promoted muscle regeneration through activation of autophagy, a process that is also critical for maintaining muscle strength. Accordingly, in old mice, ARHGEF3 depletion prevented muscle weakness by restoring autophagy flux. Collectively, our findings identify an unexpected link between ARHGEF3 and autophagy-related muscle pathophysiology.

Abstract 13433: Angiotensin II Type 2 Receptor Regulates Skeletal Myoblast Differentiation: Implications for treatment of Cachexia and Skeletal Muscle Wasting

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tadashi Yoshida ◽  
Patrice Delafontaine
Keyword(s):  
Skeletal Muscle ◽  
Angiotensin Ii ◽  
Muscle Regeneration ◽  
Muscle Wasting ◽  
Skeletal Muscle Regeneration ◽  
Myoblast Differentiation ◽  
Muscle Physiology ◽  
Ang Ii ◽  
Skeletal Muscle Wasting

Patients with advanced congestive heart failure (CHF) or chronic kidney disease (CKD) often have increased angiotensin II (Ang II) levels and cachexia. We previously demonstrated that Ang II infusion in rodents causes skeletal muscle wasting and decreases muscle regenerative potential via Ang II type 1 receptor (AT1R) signaling, likely contributing to cachexia in CHF and CKD. However, the potential role of Ang II type 2 receptor (AT2R) signaling in skeletal muscle physiology remains unknown. We found that AT2R expression was robustly increased in mouse skeletal myoblasts during differentiation, suggesting that the AT2R plays an important role in skeletal muscle regeneration. To test this hypothesis, we infused mice with AT2R antagonist PD123319 (PD, 30 mg/kg/d) or agonist CGP123319 (CGP, 1 μg/kg/min) during cardiotoxin (CTX)-induced muscle injury and regeneration. PD reduced the size of regenerating myofibers (727.5±54.6 and 516.0±37.0 μm2 in sham and PD, respectively, p<0.05) and expression of the myoblast differentiation markers myogenin and eMyHC (56.9% and 40.2% decrease in PD, respectively. p<0.01), whereas CGP had the opposite effects. siRNA mediated AT2R knockdown in mouse primary myoblasts suppressed the increase of myogenin and desmin, resulting in lowered differentiation. We analyzed changes in phosphoprotein levels in myoblasts after AT2R knockdown by phosphoprotein array and identified multiple changes, including increased phospho-ERK1/2 levels. Importantly, inhibition of ERK1/2 restored normal myoblast differentiation in the setting of AT2R knockdown, suggesting the AT2R positively regulates myoblast differentiation by reducing ERK1/2 activity. Furthermore, we found that skeletal muscle regeneration was reduced (decreased regenerating myofiber size and myogenin/desmin expression) in a mouse myocardial infarction model of CHF, concomitantly with markedly blunted increase of AT2R expression, strongly suggesting that the AT2R plays an important role in the reduction of skeletal muscle function in CHF. These data indicate that AT2R signaling positively regulates myoblast differentiation and potentiates skeletal muscle regeneration, providing a new therapeutic target in wasting disorders such as CHF and CKD.

scholarly journals Immunoneutralization of TGFβ1 Improves Skeletal Muscle Regeneration: Effects on Myoblast Differentiation and Glycosaminoglycan Content

2009 ◽  
Vol 2009 ◽  
pp. 1-16 ◽  
Author(s):  
M. Zimowska ◽  
A. Duchesnay ◽  
P. Dragun ◽  
A. Oberbek ◽  
J. Moraczewski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration ◽  
Myoblast Differentiation ◽  
In Vitro Growth ◽  
Muscle Repair ◽  
Slow Twitch ◽  
Fast Twitch

When injured by crushing, the repair of the slow-twitch soleus rat muscle, unlike the fast-twitch EDL, is associated with fibrosis. As TGFβ1, whose activity can be controlled by glycosaminoglycans (GAG), plays a major role in fibrosis, we hypothesized that levels of TGFβ1 and GAG contents could account for this differential quality of regeneration. Here we show that the regeneration of the soleus was accompanied by elevated and more sustained TGFβ1 level than in the EDL. Neutralization of TGFβ1 effects by antibodies to TGFβ1 or its receptor TGFβ-R1 improved muscle repair, especially of the soleus muscle, increased in vitro growth of myoblasts, and accelerated their differentiation. These processes were accompanied by alterations of GAG contents. These results indicate that the control of TGFβ1 activity is important to improve regeneration of injured muscle and accelerate myoblast differentiation, in part through changes in GAG composition of muscle cell environment.

scholarly journals Hsp70 Interacts with Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase 2 To Regulate p38MAPK Stability and Myoblast Differentiation during Skeletal Muscle Regeneration

2018 ◽  
Vol 38 (24) ◽  
Author(s):  
Wei Fan ◽  
Xiu Kui Gao ◽  
Xi Sheng Rao ◽  
Yin Pu Shi ◽  
Xiao Ceng Liu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Regenerative Process ◽  
Mitogen Activated Protein Kinase ◽  
Skeletal Muscle Regeneration ◽  
Myoblast Differentiation ◽  
Mitogen Activated Protein ◽  
The Stability

ABSTRACT The regenerative process of injured muscle is dependent on the fusion and differentiation of myoblasts derived from muscle stem cells. Hsp70 is important for maintaining skeletal muscle homeostasis and regeneration, but the precise cellular mechanism remains elusive. In this study, we found that Hsp70 was upregulated during myoblast differentiation. Depletion or inhibition of Hsp70/Hsc70 impaired myoblast differentiation. Importantly, overexpression of p38 mitogen-activated protein kinase α (p38MAPKα) but not AKT1 rescued the impairment of myogenic differentiation in Hsp70- or Hsc70-depleted myoblasts. Moreover, Hsp70 interacted with MK2, a substrate of p38MAPK, to regulate the stability of p38MAPK. Knockdown of Hsp70 also led to downregulation of both MK2 and p38MAPK in intact muscles and during cardiotoxin-induced muscle regeneration. Hsp70 bound MK2 to regulate MK2-p38MAPK interaction in myoblasts. We subsequently identified the essential regions required for Hsp70-MK2 interaction. Functional analyses showed that MK2 is essential for both myoblast differentiation and skeletal muscle regeneration. Taken together, our findings reveal a novel role of Hsp70 in regulating myoblast differentiation by interacting with MK2 to stabilize p38MAPK.

scholarly journals OR01-03 Thyroid Receptor Alpha Interacts with COUP-TFII in the Regulation of Postnatal Skeletal Muscle Regeneration

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Paola Aguiari ◽  
Astgik Petrosyan ◽  
Yan-Yun Liu ◽  
Sheue-Yann Cheng ◽  
Laura Perin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Orphan Receptor ◽  
Skeletal Muscle Regeneration ◽  
Myoblast Differentiation ◽  
Hormone Signaling

Abstract Myopathic changes, including muscular dystrophy and weakness, are commonly described in hypothyroid and hyperthyroid patients. Thyroid hormone signaling, via activation of thyroid nuclear receptors (TRs), plays an essential role in the maintenance of muscle mass, function, and regeneration. TRs are ligand-inducible transcription factors expressed in almost all tissues, including skeletal muscle. In a mouse model of Resistance to Thyroid Hormone carrying a frame-shift mutation in the TRα gene (TRα1PV)1,2 we observed skeletal muscle loss with aging and impaired skeletal muscle regeneration after injury. We recently described that TRα interacts with the nuclear orphan receptor Chicken Ovalbumin Upstream Promoter-factor II (COUP-TFII, or NR2F2), which is known to regulate myogenesis negatively and has a role in Duchenne-like Muscular Dystrophies3. We showed that COUP-TFII expression declines with age in WT mice, while the skeletal muscle of TRα1PV mice shows a sustained significantly higher expression of COUP-TFII. Our findings suggest that the TRα/COUP-TFII interaction might mediate the impaired skeletal muscle phenotype observed in TRα1PV mice. To better characterize this interaction, we isolated SC from 10 months old WT and TRα1PV mice and cultured them in vitro using novel methods established within our lab. Using siRNA probes, we next silenced COUP-TFII and characterized the cells via RNA-seq analysis. In vitro, we assessed myoblast differentiation and proliferation using differentiation assays and EdU incorporation. We observed that satellite cells from TRα1PV mice display impaired myoblast proliferation and in vitro myogenic differentiation compared to WT SCs. However, when COUP-TFII was silenced, the myogenic potential of TRα1PV satellite cells was restored, with a higher proliferation of myoblasts and a higher number of fully differentiated myotubes after 4 days of myogenic induction. RNAseq analysis on satellite cells from TRα1PV mice after COUP-TFII knockdown showed upregulation of genes involved in the myogenic pathway, such as Myod1 and Pax7, and of genes in the thyroid hormone signaling, such as Dio2. Ingenuity Pathway Analysis further showed activation of pathways regarding cell growth, differentiation, matrix remodeling along with muscle function, muscle contractility, and muscle contraction. These in vitro results suggest that by silencing COUP-TFII we promote the myogenic pathway and may further rescue the impaired phenotype of TRα1PV mice. These studies can help increase our knowledge of the mechanisms involved in thyroid hormone signaling in skeletal muscle regeneration, which will ultimately increase the possibility of designing more specific treatments for patients with thyroid hormone-induced myopathies. References: 1Milanesi, A., et al, Endocrinology 2016; 2Kaneshige, M. et al, Proc Natl Acad Sci U S 2001; 3Lee HJ, et al, Sci Rep. 2017.

scholarly journals Circular RNA profiling of buffalo myoblasts reveals an abundant circPICALM that promotes myoblast differentiation

2020 ◽  
Author(s):  
Mingming Song ◽  
Mengjie Chen ◽  
Kongwei Huang ◽  
Dandan Zhong ◽  
Yaling Chen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Muscle Development ◽  
Expression Profiles ◽  
Muscle Growth ◽  
Circular Rna ◽  
Skeletal Muscle Regeneration ◽  
Myoblast Differentiation ◽  
Circular Rnas

Abstract Background Muscle development is a precisely orchestrated and complex process, and circular RNAs (circRNAs) has been demonstrated to play important roles in skeletal muscle growth and development. However, the regulatory functions of circRNA during buffalo muscle developmental processes have not been understood.Results In this study, Ribo-Zero RNA-Seq was performed to investigate the circRNAs expression profiles of proliferated and differentiated buffalo myoblasts. A stringent set of 3,142 circRNAs was finally characterized. Comparing the expression profiles of circRNAs revealed that 110 circRNAs were expressed differentially during myoblast differentiation. We focused on the role of a candidate circRNA, which was named circPICALM based on its host gene PICALM, and was highly (but differentially) expressed in proliferated and differentiated myoblasts. Flow cytometry, EdU incorporation, and Western blotting assays demonstrate that circPICALM promoted myoblasts proliferation and inhibited cells apoptosis. Moreover, overexpression of circPICALM promoted the differentiation of primary buffalo myoblasts. Moreover, circPICALM in vivo stimulated skeletal muscle regeneration in cardiotoxin-induced muscle injury. The RNA pulldown results showed that circPICALM could capture TUBA1B protein, revealing that circPICALM might exert its biological function by binding TUBA1B protein. Conclusions These results demonstrate that the novel non-coding regulator circPICALM induces myoblast differentiation and skeletal muscle regeneration.

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