scholarly journals Androgen receptor regulates the proliferation of myoblasts under appropriate or excessive stretch through IGF-1 receptor mediated p38 and ERK1/2 pathways

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Shaoting Fu ◽  
Xiaojing Lin ◽  
Lijun Yin ◽  
Xiaohui Wang
Keyword(s):  
Androgen Receptor ◽  
Muscle Mass ◽  
Satellite Cells ◽  
C2c12 Cells ◽  
C2c12 Myoblasts ◽  
Excessive Exercise ◽  
L6 Cells ◽  
Proliferation And Differentiation ◽  
Exercise Induced ◽  
P38 Pathway

Abstract Background Androgen receptor (AR) exerts important roles in exercise-induced alterations of muscle mass, in which the proliferation and differentiation of satellite cells or myoblasts are crucial. Our previous study in C2C12 myoblasts demonstrated that 15% (mimic appropriate exercise) and 20% (mimic excessive exercise) stretches promoted and inhibited the proliferation respectively; and AR played a crucial role in 15% stretch-induced pro-proliferation through IGF-1-modulated PI3K/Akt, p38 and ERK1/2 pathways, but AR’s role in stretches-modulated proliferation of general myoblasts, especially 20% stretch, remains unclear, and the mechanisms need to be further clarified. Methods Firstly, the discrepancy in proliferation and the above indicators between L6 (without AR) and C2C12 (with AR) myoblasts were compared under 15% or 20% stretch. Then the influences of transfection AR or exogenous IGF-1 treatment on proliferation and these indicators were detected in stretched L6 myoblasts. Results (1) Under un-stretched state, the proliferation of L6 was slower than C2C12 cells. Furthermore, AR knockdown in C2C12 myoblasts repressed, while AR overexpression in L6 myoblasts promoted the proliferation. (2) 15% stretch-induced increases in the proliferation and activities of p38 and ERK1/2 were lower in L6 than C2C12 cells; AR overexpression enhanced the proliferation of 15% stretched L6 cells accompanied with the increases of p38 and ERK1/2 activities. (3) 20% stretch-induced anti-proliferation and inhibition of p38 activity were severer in L6 than C2C12 myoblasts; AR overexpression reversed the anti-proliferation of 20% stretch and enhanced p38 activity in L6 myoblasts. (4) In stretched L6 myoblasts, AR overexpression increased IGF-1R level despite no detectable IGF-1; and recombinant IGF-1 increased the proliferation, the level of IGF-1R, and the activities of p38 and ERK1/2 in 15% stretched L6 myoblasts. Conclusions The study demonstrated AR's crucial roles in stretches-regulated proliferation of myoblasts, and increased AR fulfilled 15% stretch's pro-proliferation via activating IGF-1R- p38 and ERK1/2 pathways while decreased AR achieved 20% stretch's anti-proliferation via inhibiting IGF-1R- p38 pathway, which is useful to understand in depth the role and mechanisms of AR in appropriate exercise increasing while excessive exercise decreasing muscle mass.

scholarly journals Androgen Receptor Regulates the Proliferation of Stretched Myoblasts and Its Mechanisms: IGF-1R-mediated p38 and ERK1/2 Pathways

2020 ◽  
Author(s):  
Shaoting Fu ◽  
Xiaojing Lin ◽  
Lijun Yin ◽  
Xiaohui Wang
Keyword(s):  
Androgen Receptor ◽  
Proliferation Rate ◽  
C2c12 Cells ◽  
Dependent Manner ◽  
C2c12 Myoblasts ◽  
Excessive Exercise ◽  
L6 Cells ◽  
Sirna Interference ◽  
Dose Dependent ◽  
P38 Pathway

Abstract BackgroundOur previous study has indicated that in C2C12 myoblasts androgen receptor (AR) plays a crucial role in 15% stretch-induced proliferation through insulin-like growth factor (IGF-1)-modulated PI3K/Akt, p38 and ERK1/2 pathways. In this study we further explored AR's effects on 15% and 20% stretches-modulated myoblasts proliferation and involved pathways in L6 (no detectable AR) and C2C12 (abundant AR) myoblasts.MethodsThe proliferation and the above indicators were compared between stretched L6 and C2C12 myoblasts by CCK8, ELISA and Western blot, then were detected again in stretched L6 myoblasts after transfection with AR overexpression plasmid utilizing LipoPlusTM 2000 reagent or treatment with different concentrations (200, 500, 1000 ng/ml) IGF-1 recombinant polypeptide.ResultsWe found that ①Under un-stretched states, the proliferation rate of L6 cells was slower than that of C2C12 cells, and the proliferation of C2C12 cells was repressed by AR knockdown using siRNA interference, while L6 myoblasts proliferation was promoted by overexpression AR. ②The proliferation rate as well as the activities of p38 and ERK1/2 increased by 15% stretch were much lower in L6 than that in C2C12 cells; AR overexpression enhanced the proliferation of 15% stretched L6 cells accompanied with increased activities of p38 and ERK1/2; ③20% stretch decreased the proliferation and activity of p38 in L6 more than that in C2C12 myoblasts; overexpression of AR totally reversed the anti-proliferation of 20% stretch and significantly enhanced p38 activity in L6 myoblasts;④In L6 myoblasts, overexpression AR increased IGF-1R expression despite no detectable IGF-1 was secreted; and recombinant IGF-1 increased not only the proliferation, but also the protein level of IGF-1R and activities of p38 and ERK1/2 in a dose-dependent manner in 15% stretched L6 myoblasts. ConclusionsAR fulfilled 15% stretch-induced pro-proliferation of myoblasts by activating IGF-1R-p38 and ERK1/2 pathways, while 20% stretch-induced anti-proliferation was mediated by inhibiting AR-IGF-1R-p38 pathway. This study is beneficial to understand in depth the role and mechanisms of AR on appropriate exercise increases while excessive exercise decreases muscle mass.

Mixed lactate and caffeine compound increases satellite cell activity and anabolic signals for muscle hypertrophy

2015 ◽  
Vol 118 (6) ◽  
pp. 742-749 ◽  
Author(s):  
Yoshimi Oishi ◽  
Hayato Tsukamoto ◽  
Takumi Yokokawa ◽  
Keisuke Hirotsu ◽  
Mariko Shimazu ◽  
...  
Keyword(s):  
Satellite Cells ◽  
Cell Activity ◽  
Treadmill Running ◽  
C2c12 Cells ◽  
Protein Levels ◽  
Low Intensity ◽  
Proliferation And Differentiation ◽  
Total Dna ◽  
Low Intensity Exercise

We examined whether a mixed lactate and caffeine compound (LC) could effectively elicit proliferation and differentiation of satellite cells or activate anabolic signals in skeletal muscles. We cultured C2C12 cells with either lactate or LC for 6 h. We found that lactate significantly increased myogenin and follistatin protein levels and phosphorylation of P70S6K while decreasing the levels of myostatin relative to the control. LC significantly increased protein levels of Pax7, MyoD, and Ki67 in addition to myogenin, relative to control. LC also significantly increased follistatin expression relative to control and stimulated phosphorylation of mTOR and P70S6K. In an in vivo study, male F344/DuCrlCrlj rats were assigned to control (Sed, n = 10), exercise (Ex, n = 12), and LC supplementation (LCEx, n = 13) groups. LC was orally administered daily. The LCEx and Ex groups were exercised on a treadmill, running for 30 min at low intensity every other day for 4 wk. The LCEx group experienced a significant increase in the mass of the gastrocnemius (GA) and tibialis anterior (TA) relative to both the Sed and Ex groups. Furthermore, the LCEx group showed a significant increase in the total DNA content of TA compared with the Sed group. The LCEx group experienced a significant increase in myogenin and follistatin expression of GA relative to the Ex group. These results suggest that administration of LC can effectively increase muscle mass concomitant with elevated numbers of myonuclei, even with low-intensity exercise training, via activated satellite cells and anabolic signals.

scholarly journals Activation of Cdc6 by MyoD is associated with the expansion of quiescent myogenic satellite cells

2010 ◽  
Vol 188 (1) ◽  
pp. 39-48 ◽  
Author(s):  
Keman Zhang ◽  
Jingfeng Sha ◽  
Marian L. Harter
Keyword(s):  
Stem Cells ◽  
Satellite Cells ◽  
S Phase ◽  
Transcriptional Factor ◽  
C2c12 Cells ◽  
C2c12 Myoblasts ◽  
Muscle Stem Cells ◽  
Primary Mouse ◽  
E Box ◽  
Myogenic Satellite Cells

MyoD is a transcriptional factor that is required for the differentiation of muscle stem cells (satellite cells). In this study, we describe a previously unknown function for MyoD in regulating a gene (Cdc6) that is vital to endowing chromatin with the capability of replicating DNA. In C2C12 and primary mouse myoblasts, we show that MyoD can occupy an E-box within the promoter of Cdc6 and that this association, along with E2F3a, is required for its activity. MyoD and Cdc6 are both expressed after quiescent C2C12 myoblasts or satellite cells in association with myofibers are stimulated for growth, but MyoD appears at least 2–3 h earlier than Cdc6. Finally, knockdown of MyoD impairs the ability of C2C12 cells to express Cdc6 after leaving quiescence, and as a result, they cannot fully progress into S phase. Our results define a mechanism by which MyoD helps myogenic satellite cells to enter into the first round of DNA replication after transitioning out of quiescence.

scholarly journals miR-21-5p Regulates the Proliferation and Differentiation of Skeletal Muscle Satellite Cells by Targeting KLF3 in Chicken

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 814
Author(s):  
Donghao Zhang ◽  
Jinshan Ran ◽  
Jingjing Li ◽  
Chunlin Yu ◽  
Zhifu Cui ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Muscle Development ◽  
Target Genes ◽  
Cell Number ◽  
Sequencing Data ◽  
Proliferation Markers ◽  
Muscle Satellite Cells ◽  
Skeletal Muscle Satellite Cells ◽  
Proliferation And Differentiation

The proliferation and differentiation of skeletal muscle satellite cells (SMSCs) play an important role in the development of skeletal muscle. Our previous sequencing data showed that miR-21-5p is one of the most abundant miRNAs in chicken skeletal muscle. Therefore, in this study, the spatiotemporal expression of miR-21-5p and its effects on skeletal muscle development of chickens were explored using in vitro cultured SMSCs as a model. The results in this study showed that miR-21-5p was highly expressed in the skeletal muscle of chickens. The overexpression of miR-21-5p promoted the proliferation of SMSCs as evidenced by increased cell viability, increased cell number in the proliferative phase, and increased mRNA and protein expression of proliferation markers including PCNA, CDK2, and CCND1. Moreover, it was revealed that miR-21-5p promotes the formation of myotubes by modulating the expression of myogenic markers including MyoG, MyoD, and MyHC, whereas knockdown of miR-21-5p showed the opposite result. Gene prediction and dual fluorescence analysis confirmed that KLF3 was one of the direct target genes of miR-21-5p. We confirmed that, contrary to the function of miR-21-5p, KLF3 plays a negative role in the proliferation and differentiation of SMSCs. Si-KLF3 promotes cell number and proliferation activity, as well as the cell differentiation processes. Our results demonstrated that miR-21-5p promotes the proliferation and differentiation of SMSCs by targeting KLF3. Collectively, the results obtained in this study laid a foundation for exploring the mechanism through which miR-21-5p regulates SMSCs.

MiR-222-3p Regulates the Proliferation and Differentiation of C2C12 Myoblasts by Targeting BTG2

2019 ◽  
Vol 53 (1) ◽  
pp. 38-44
Author(s):  
D. L. Yang ◽  
M. L. Gan ◽  
Y. Tan ◽  
G. H. Ge ◽  
Q. Li ◽  
...  
Keyword(s):  
C2c12 Myoblasts ◽  
Proliferation And Differentiation

Transthyretin contributes to insulin resistance and diminishes exercise-induced insulin sensitivity in obese mice by inhibiting AMPK activity in skeletal muscle

2021 ◽  
Author(s):  
Yingzi He ◽  
Ruojun Qiu ◽  
Beibei Wu ◽  
Weiwei Gui ◽  
Xihua Lin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Inhibitory Effect ◽  
Quadriceps Femoris ◽  
Treadmill Training ◽  
C2c12 Cells ◽  
Obese Mice ◽  
Insulin Resistant ◽  
Ampk Activity ◽  
Exercise Induced

Exercise improves obesity-induced insulin resistance and metabolic disorders via mechanisms that remain unclear. Here, we show that the levels of the hepatokine transthyretin (TTR) in circulation are elevated in insulin-resistant individuals including high-fat diet (HFD)-induced obese mice, db/db mice, and patients with metabolic syndrome. Liver Ttr mRNA and circulating TTR levels were reduced in mice by treadmill training, as was the TTR levels in quadriceps femoris muscle; however, AMPK signalling activity was enhanced. Transgenic overexpression of TTR or injection of purified TTR triggered insulin resistance in mice fed on regular chow (RC). Furthermore, TTR overexpression reduced the beneficial effects of exercise on insulin sensitivity in HFD-fed mice. TTR was internalized by muscle cells via the membrane receptor Grp78 and the internalization into the quadriceps femoris was reduced by treadmill training. The TTR/Grp78 combination in C2C12 cells was increased, whereas the AMPK activity of C2C12 cells was decreased as the TTR concentration rose. Additionally, Grp78 silencing prevented the TTR internalization and reversed its inhibitory effect on AMPK activity in C2C12 cells. Our study suggests that elevated circulating TTR may contribute to insulin resistance and counteract the exercise-induced insulin sensitivity improvement; the TTR suppression might be an adaptive response to exercise through enhancing AMPK activity in skeletal muscles.

Overload-induced androgen receptor expression in the aged rat hindlimb receiving nandrolone decanoate

2003 ◽  
Vol 94 (3) ◽  
pp. 1153-1161 ◽  
Author(s):  
Won Jun Lee ◽  
Joseph McClung ◽  
G. A. Hand ◽  
James A. Carson
Keyword(s):  
Androgen Receptor ◽  
Muscle Mass ◽  
Protein Concentration ◽  
Muscle Protein ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Nandrolone Decanoate ◽  
Muscle Weight ◽  
Aged Rat ◽  
Androgen Receptor Protein

This study's purpose was to examine whether functional overload with nandrolone decanoate (ND) administration increased muscle mass and steroid receptor concentration in aged rat soleus (Sol) and plantaris (Plan) muscle. ND (6 mg/kg body wt) was administered once a week for 4 wk, whereas control rats received sesame seed oil injections. Functional overload of the hindlimb Sol and Plan was induced by synergistic gastrocnemius muscle ablation at the beginning of the fourth week. Adult (5 mo of age) and aged rats (25 mo of age) were randomly assigned to four groups: control, overload, control-ND, and overload-ND. Seven days of functional overload increased adult Sol muscle mass 27%, whereas the aged Sol muscle mass did not change. The aged overloaded Sol muscle receiving ND significantly increased muscle weight by 35% and total muscle protein by 24%. Aged Plan muscle did not increase muscle weight with overload or ND treatment. Androgen receptor protein was induced by ND treatment and functional Ov, and combining the two treatments induced Sol androgen receptor protein concentration above either alone. Sol glucocorticoid receptor protein concentration increased in overload groups of both ages. ND administration can increase aged Sol muscle mass and protein content after 7 days of functional overload, and the cooperative induction of androgen receptor may be important for this response.

Interleukin-6 promotes myogenic differentiation of mouse skeletal muscle cells: role of the STAT3 pathway

2013 ◽  
Vol 304 (2) ◽  
pp. C128-C136 ◽  
Author(s):  
Miriam Hoene ◽  
Heike Runge ◽  
Hans Ulrich Häring ◽  
Erwin D. Schleicher ◽  
Cora Weigert
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Myogenic Differentiation ◽  
Muscle Cells ◽  
C2c12 Cells ◽  
Skeletal Muscle Cells ◽  
Wild Type ◽  
C2c12 Myoblasts ◽  
Sequence Of Events ◽  
Primary Mouse

Myogenic differentiation of skeletal muscle cells is characterized by a sequence of events that include activation of signal transducer and activator of transcription 3 (STAT3) and enhanced expression of its target gene Socs3. Autocrine effects of IL-6 may contribute to the activation of the STAT3-Socs3 cascade and thus to myogenic differentiation. The importance of IL-6 and STAT3 for the differentiation process was studied in C2C12 cells and in primary mouse wild-type and IL-6−/− skeletal muscle cells. In differentiating C2C12 myoblasts, the upregulation of IL-6 mRNA expression and protein secretion started after increased phosphorylation of STAT3 on tyrosine 705 and increased mRNA expression of Socs3 was observed. Knockdown of STAT3 and IL-6 mRNA in differentiating C2C12 myoblasts impaired the expression of the myogenic markers myogenin and MyHC IIb and subsequently myotube fusion. However, the knockdown of IL-6 did not prevent the induction of STAT3 tyrosine phosphorylation. The IL-6-independent activation of STAT3 was verified in differentiating primary IL-6−/− myoblasts. The phosphorylation of STAT3 and the expression levels of STAT3, Socs3, and myogenin during differentiation were comparable in the primary myoblasts independent of the genotype. However, IL-6−/− cells failed to induce MyHC IIb expression to the same level as in wild-type cells and showed reduced myotube formation. Supplementation of IL-6 could partially restore the fusion of IL-6−/− cells. These data demonstrate that IL-6 depletion during myogenic differentiation does not reduce the activation of the STAT3-Socs3 cascade, while IL-6 and STAT3 are both necessary to promote myotube fusion.

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