scholarly journals Stimulative Effects of Low Intensity He-Ne Laser Irradiation on the Proliferative Potential and Cell-Cycle Progression of Myoblasts in Culture

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Cui-Ping Zhang ◽  
Shao-Dan Li ◽  
Yan Chen ◽  
Yan-Ming Jiang ◽  
Peng Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Skeletal Muscle ◽  
Laser Irradiation ◽  
Muscle Regeneration ◽  
Cell Cycle Progression ◽  
Growth Potential ◽  
Control Group ◽  
Cycle Progression ◽  
Adult Skeletal Muscle ◽  
Low Intensity

Low intensity laser irradiation (LILI) was found to promote the regeneration of skeletal musclein vivobut the cellular mechanisms are not fully understood. Myoblasts, normally quiescent and inactivated in adult skeletal muscle, are a type of myogenic progenitor cells and considered as the major candidates responsible for muscle regeneration. The aim of the present study was to study the effect of LILI on the growth potential and cell-cycle progression of the cultured myoblasts. Primary myoblasts isolated from rat hind legs were cultured in nutrient-deficient medium for 36 hours and then irradiated by helium-neon laser at a certain energy density. Immunohistochemical and flow cytometric analysis revealed that laser irradiation could increase the expression of cellular proliferation marker and the amount of cell subpopulations in the proliferative phase as compared with the nonirradiated control group. Meanwhile, the expressions of cell-cycle regulatory proteins in the laser-treated myoblasts were markedly upregulated as compared to the unirradiated cells, indicating that LILI could promote the reentry of quiescent myoblasts into the cell division cycle. These results suggest that LILI at certain fluences could promote their proliferation, thus contributing to the skeletal muscle regeneration following trauma and myopathic diseases.

scholarly journals Foxk1 recruits the Sds3 complex and represses gene expression in myogenic progenitors

2012 ◽  
Vol 446 (3) ◽  
pp. 349-357 ◽  
Author(s):  
Xiaozhong Shi ◽  
David C. Seldin ◽  
Daniel J. Garry
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Skeletal Muscle ◽  
Protein Kinase ◽  
Muscle Regeneration ◽  
Cell Cycle Progression ◽  
Adaptor Protein ◽  
Skeletal Muscle Regeneration ◽  
Cycle Progression ◽  
Repression Complex

Previous studies have established that Foxk1 (forkhead box k1) plays an important role in skeletal muscle regeneration. Foxk1 regulates the cell-cycle progression of myogenic progenitors by repressing the cell-cycle inhibitor gene p21. However, the underlying mechanism is not well understood. In the present study, we report the identification of Sds3 (suppressor of defective silencing 3) as an adaptor protein that recruits the Sin3 [SWI (switch)-independent 3]–HDAC (histone deacetylase) repression complex and binds Foxk1. Using GST (glutathione transferase) pull-down assays, we defined the interaction between the Foxk1 FHA (forkhead-associated domain) domain and phospho-Thr49 in Sds3. We demonstrated that the transcriptional repression of Foxk1 is dependent on the Sin3–Sds3 repression complex, and knockdown of Sds3 results in cell-cycle arrest. We further identified the protein kinase CK2 as the protein kinase for Sds3 Thr49 and demonstrated that the protein kinase activity of CK2 is required for proper cell-cycle progression. Analysis of CK2 mutant mice reveals perturbation of skeletal muscle regeneration due to the dysregulation of cell-cycle kinetics. Overall, these studies define a CK2–Sds3–Foxk1 cascade that modulates gene expression and regulates skeletal muscle regeneration.

scholarly journals Tumor Necrosis Factor Alpha Regulates Skeletal Myogenesis by Inhibiting SP1 Interaction with cis-Acting Regulatory Elements within the Fbxl2 Gene Promoter

2020 ◽  
Vol 40 (12) ◽  
Author(s):  
Michael E. O’Brien ◽  
James Londino ◽  
Marcus McGinnis ◽  
Nathaniel Weathington ◽  
Jessica Adair ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Cell Cycle Progression ◽  
Myogenic Differentiation ◽  
Core Promoter ◽  
Skeletal Muscle Regeneration ◽  
Skeletal Myogenesis ◽  
Necrosis Factor Alpha ◽  
Tnf Α

ABSTRACT FBXL2 is an important ubiquitin E3 ligase component that modulates inflammatory signaling and cell cycle progression, but its molecular regulation is largely unknown. Here, we show that tumor necrosis factor alpha (TNF-α), a critical cytokine linked to the inflammatory response during skeletal muscle regeneration, suppressed Fbxl2 mRNA expression in C2C12 myoblasts and triggered significant alterations in cell cycle, metabolic, and protein translation processes. Gene silencing of Fbxl2 in skeletal myoblasts resulted in increased proliferative responses characterized by activation of mitogen-activated protein (MAP) kinases and nuclear factor kappa B and decreased myogenic differentiation, as reflected by reduced expression of myogenin and impaired myotube formation. TNF-α did not destabilize the Fbxl2 transcript (half-life [t1/2], ∼10 h) but inhibited SP1 transactivation of its core promoter, localized to bp −160 to +42 within the proximal 5′ flanking region of the Fbxl2 gene. Chromatin immunoprecipitation and gel shift studies indicated that SP1 interacted with the Fbxl2 promoter during cellular differentiation, an effect that was less pronounced during proliferation or after TNF-α exposure. TNF-α, via activation of JNK, mediated phosphorylation of SP1 that impaired its binding to the Fbxl2 promoter, resulting in reduced transcriptional activity. The results suggest that SP1 transcriptional activation of Fbxl2 is required for skeletal muscle differentiation, a process that is interrupted by a key proinflammatory myopathic cytokine. IMPORTANCE Skeletal muscle regeneration and repair involve the recruitment and proliferation of resident satellite cells that exit the cell cycle during the process of myogenic differentiation to form myofibers. We demonstrate that the ubiquitin E3 ligase subunit FBXL2 is essential for skeletal myogenesis through its important effects on cell cycle progression and cell proliferative signaling. Further, we characterize a new mechanism whereby sustained stimulation by a major proinflammatory cytokine, TNF-α, regulates skeletal myogenesis by inhibiting the interaction of SP1 with the Fbxl2 core promoter in proliferating myoblasts. Our findings contribute to the understanding of skeletal muscle regeneration through the identification of Fbxl2 as both a critical regulator of myogenic proliferative processes and a susceptible gene target during inflammatory stimulation by TNF-α in skeletal muscle. Modulation of Fbxl2 activity may have relevance to disorders of muscle wasting associated with sustained proinflammatory signaling.

scholarly journals p21-Activated Kinase 4 Promotes Intimal Hyperplasia and Vascular Smooth Muscle Cells Proliferation during Superficial Femoral Artery Restenosis after Angioplasty

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Liangxi Yuan ◽  
Xianli Duan ◽  
Jian Dong ◽  
Qingsheng Lu ◽  
Jian Zhou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle Cells ◽  
Femoral Artery ◽  
Cell Cycle Progression ◽  
Control Group ◽  
Cycle Progression ◽  
P21 Activated Kinase ◽  
Experimental Group ◽  
Vsmcs Proliferation

The aim of this study is to explore the function of p21-activated kinase 4 (PAK4) in intimal hyperplasia (IH) and vascular smooth muscle cells (VSMCs) proliferation. We choose vascular samples from patients undergoing angioplasty in superficial femoral artery (SFA) as the experimental group and vascular samples from donors without clinical SFA restenosis as the control group, respectively. We draw from the results that both levels of mRNA and protein of PAK4 in the experimental group increased dramatically compared with the control group. IH arose from angioplasty of SFA. Moreover, overexpression of PAK4 dramatically contributed to cell proliferation of VSMCs and promoted cell cycle progression from G0/G1 phase (71.12±0.69% versus 58.77±0.77%, P<0.001) into S phase (23.99±0.21% versus 31.35±0.33%, P<0.001). Besides, PAK4 downregulated the level of p21 and enhanced the activity of Akt as well. And we conclude that PAK4 acts as a regulator of cell cycle progression of VSMC by mediating Akt signaling and controlling p21 levels, which further modulate IH and VSMCs’ proliferation.

Abnormal apoptosis and cell cycle progression in humans exposed to methyl tertiary-butyl ether and benzene contaminating water

1997 ◽  
Vol 16 (9) ◽  
pp. 485-494 ◽  
Author(s):  
Aristo Vojdani ◽  
Eli Mordechai ◽  
Nachman Brautbar
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Control Level ◽  
Control Group ◽  
Pyrrolidine Dithiocarbamate ◽  
Cycle Progression ◽  
Tertiary Butyl

1 In this study we hypothesized that in individuals with certain genetic makeup, MTBE, benzene or their metabolites act as adducts and may induce pro grammed cell death. 2 Our study involved a group of 60 male and female subjects who were exposed to MTBE and benzene- 5 contaminated water concentrations up to 76 PPB for MTBE and 14 PPB for benzene, for a period of 5 to 8 years. For comparison, we recruited a control group consisting of 32 healthy males and females with similar age distribution and without a history of exposure to MTBE or benzene. 3 Peripheral blood lymphocytes (PBL) of both groups were tested for the percentage of apoptotic cells and cell cycle progression using flow cytometry. 4 When apoptotic lymphocytes from exposed indivi duals were compared to apoptotic lymphocytes from the control group, statistically-significant differences between each mean group were detected (26.4 ± 1.8 and 12.1 ± 1.3, respectively), indicating an increased rate of apoptosis in 80.5% of exposed individuals ( P<0.0001, Mann-Whitney U-Test). MTBE and ben- a zene-induced apoptosis is attributed to a discrete block within the cell cycle progression. Because cell cycle analysis showed that in PBL from chemically-exposed individuals, between 20-50% of cells were accumu lated at the S-G2/M boundaries. One of the signaling molecules which mediates programmed cell death is nuclear factor Kappa-B (NF-kB). NF-kB was examined as one of the many molecular mechanisms for mediating cell death by MTBE and benzene. Indeed, addition of inhibitors of NF-kB activation pyrrolidine dithiocarbamate (PDTC), to the lymphocytes of the chemically-exposed group was capable of inhibiting programmed cell death by 40%. This reversal of apoptosis almost to the control level by inhibitor of NF-kB activation may indicate involvement of this signaling molecule in MTBE and benzene induction of programmed cell death.

scholarly journals Rho-associated Protein Kinase 2 Confers Epileptogenesis through the Activation of Astroglial Stat3 Pathway

2020 ◽  
Author(s):  
Li-jia Song ◽  
Hua Zhang ◽  
Jun-gong Jin ◽  
Chao Wang ◽  
Xiao-Peng Qu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
Expression Profiles ◽  
Control Group ◽  
Drug Resistant ◽  
Cycle Progression ◽  
Stat3 Pathway

Abstract Patients with temporal lobe epilepsy (TLE) are prone to tolerance to antiepileptic drugs. Based on the perspective of molecular targets for drug resistance, it is necessary to explore effective drug resistant genes and signaling pathways for the treatment of TLE. We performed gene expression profiles in hippocampus of patients with drug-resistant TLE and identified ROCK2 as one of the 20 most significantly increased genes in hippocampus. In vitro and in vivo experiments were performed to identify the potential role of ROCK2 in epileptogenesis. In addition, the activity of Stat3 pathway was tested in hippocampal tissues and primary cultured astrocytes. The expression levels of ROCK2 in the hippocampus of TLE patients were significantly increased compared with the control group, which was due to the hypomethylation of ROCK2 promoter. Fasudil, a specific Rho-kinase inhibitor, alleviated epileptic seizures in the pilocarpine rat model of TLE. Furthermore, ROCK2 activated the Stat3 pathway in pilocarpine-treated epilepsy rats, and the spearman correlation method confirmed that ROCK2 is associated with Stat3 activation in TLE patients. In addition, ROCK2 was predominantly expressed in astrocytes during epileptogenesis, and induced epileptogenesis by activating astrocyte cell cycle progression via Stat3 pathway. The overexpressed ROCK2 plays an important role in the pathogenesis of drug-resistant epilepsy. ROCK2 accelerates astrocytes cell cycle progression via the activation of Stat3 pathway likely provides the key to explaining the process of epileptogenesis.

scholarly journals Establishing cell-intrinsic limitations in cell cycle progression controls graft growth and promotes differentiation of pancreatic endocrine cells

2020 ◽  
Author(s):  
Lina Sui ◽  
Yurong Xin ◽  
Daniela Georgieva ◽  
Giacomo Diedenhofen ◽  
Leena Haataja ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Endocrine Cells ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Growth Potential ◽  
Proliferative Potential ◽  
G1 Arrest ◽  
Cycle Progression

AbstractLimitations in cell proliferation are a key barrier to reprogramming differentiated cells to pluripotent stem cells, and conversely, acquiring these limitations may be important to establish the differentiated state. The pancreas, and beta cells in particular have a low proliferative potential, which limits regeneration, but how these limitations are established is largely unknown. Understanding proliferation potential is important for the safty of cell replacement therapy with cell products made from pluripotent stem cell which have unlimited proliferative potential. Here we test a novel hypothesis, that these limitations are established through limitations in S-phase progression. We used a stem cell-based system to expose differentiating stem cells to small molecules that interfere with cell cycle progression either by inducing G1 arrest, impairing S-phase entry, or S-phase completion. Upon release from these molecules, we determined growth potential, differentiation and function of insulin-producing endocrine cells both in vitro and after grafting in vivo. We found that the combination of G1 arrest with a compromised ability to complete DNA replication promoted the differentiation of pancreatic progenitor cells towards insulin-producing cells, improved the stability of the differentiated state, and protected mice from diabetes without the formation of cystic growths. Therefore, a compromised ability to enter S-phase and replicate the genome is a functionally important property of pancreatic endocrine differentiation, and can be exploited to generate insulin-producing organoids with predictable growth potential after transplantation.

scholarly journals Muscle Satellite Cell Heterogeneity: Does Embryonic Origin Matter?

2021 ◽  
Vol 9 ◽  
Author(s):  
Lara Rodriguez-Outeiriño ◽  
Francisco Hernandez-Torres ◽  
F. Ramírez-de Acuña ◽  
Lidia Matías-Valiente ◽  
Cristina Sanchez-Fernandez ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Lineage Tracing ◽  
Skeletal Muscle Regeneration ◽  
Quiescent State ◽  
Functional Heterogeneity ◽  
Adult Skeletal Muscle ◽  
Homeostatic Process

Muscle regeneration is an important homeostatic process of adult skeletal muscle that recapitulates many aspects of embryonic myogenesis. Satellite cells (SCs) are the main muscle stem cells responsible for skeletal muscle regeneration. SCs reside between the myofiber basal lamina and the sarcolemma of the muscle fiber in a quiescent state. However, in response to physiological stimuli or muscle trauma, activated SCs transiently re-enter the cell cycle to proliferate and subsequently exit the cell cycle to differentiate or self-renew. Recent evidence has stated that SCs display functional heterogeneity linked to regenerative capability with an undifferentiated subgroup that is more prone to self-renewal, as well as committed progenitor cells ready for myogenic differentiation. Several lineage tracing studies suggest that such SC heterogeneity could be associated with different embryonic origins. Although it has been established that SCs are derived from the central dermomyotome, how a small subpopulation of the SCs progeny maintain their stem cell identity while most progress through the myogenic program to construct myofibers is not well understood. In this review, we synthesize the works supporting the different developmental origins of SCs as the genesis of their functional heterogeneity.

scholarly journals The Antimicrobial Peptide Nal-P-113 Exerts a Reparative Effect by Promoting Cell Proliferation, Migration, and Cell Cycle Progression

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Nana Liu ◽  
Shuo Guan ◽  
Hongyan Wang ◽  
Chen Li ◽  
Jyawei Cheng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Antimicrobial Peptide ◽  
Cell Cycle Progression ◽  
Control Group ◽  
Blank Control Group ◽  
Cycle Progression ◽  
Immunohistochemical Assay ◽  
And Migration ◽  
Proliferation And Migration

Objective. The primary purpose of this study was to evaluate the reparative efficacy of a novel antimicrobial peptide, Nal-P-113, in shortening the healing time of oral mucosal ulcers by promoting cell proliferation and migration and accelerating the cell cycle. Methods. Cell counting kit-8 (CCK-8) and wound-healing assays were used to evaluate the proliferation and migration of human immortalized oral epithelial cells (HIOECs). The cell cycle distribution of HIOECs was analyzed by flow cytometry. Additionally, the RNA levels of EGF, FGF-2, and TGF-β1 of HIOECs were assessed by real-time PCR. Rats were divided into three groups randomly: (a) blank control group; (b) 20 μg/mL Nal-P-113; and (c) 10 ng/mL rhEGF. An oral mucosal ulcer was induced in every rat by the application of 30% acetic acid. An immunohistochemical assay was used to assess the expression of EGF, FGF-2, and TGF-β1 in the rat oral mucosa. Results. In the CCK-8 assay, the optical density values in the Nal-P-113 and rhEGF groups were found to be significantly higher than that in the blank control group. In addition, the scratch areas in the Nal-P-113 and rhEGF groups were found to be significantly smaller (P<0.05). Cell cycle analysis showed that Nal-P-113 accelerated the entry of HIOECs into the S phase and expedited their cell cycles. The RT-PCR results suggested that Nal-P-113 upregulated the RNA levels of EGF and FGF-2 but downregulated that of TGF-β1 at 24 h and 48 h. Lastly, the immunohistochemical assay verified that Nal-P-113 changed the expression of the above cytokines in rat mucosal ulcers. Conclusion. Nal-P-113 promoted the repair of oral mucosal ulcers by increasing the EGF and FGF-2 expression and decreasing that of TGF-β1 in HIOECs, accelerating their proliferation and cell cycle progression. The application of Nal-P-113 might serve as an effective therapeutic approach for recurrent aphthous stomatitis.

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