scholarly journals IL-1β and TNF-α Modulation of Proliferated and Committed Myoblasts: IL-6 and COX-2-Derived Prostaglandins as Key Actors in the Mechanisms Involved

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2005
Author(s):  
Angela M. Alvarez ◽  
Carlos DeOcesano-Pereira ◽  
Catarina Teixeira ◽  
Vanessa Moreira
Keyword(s):  
Cell Proliferation ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration ◽  
Myoblast Differentiation ◽  
Tnf Α ◽  
Cox 2 ◽  
Myoblast Cells ◽  
Inflammatory Signalling ◽  
Mouse Myoblast

In this study, we investigated the effects and mechanisms of the pro-inflammatory cytokines IL-1β and TNF-α on the proliferation and commitment phases of myoblast differentiation. C2C12 mouse myoblast cells were cultured to reach a proliferated or committed status and were incubated with these cytokines for the evaluation of cell proliferation, cyclooxygenase 2 (COX-2) expression, release of prostaglandins (PGs) and myokines, and activation of myogenic regulatory factors (MRFs). We found that inhibition of the IL-6 receptor reduced IL-1β- and TNF-α-induced cell proliferation, and that the IL-1β effect also involved COX-2-derived PGs. Both cytokines modulated the release of the myokines myostatin, irisin, osteonectin, and IL-15. TNF-α and IL-6 reduced the activity of Pax7 in proliferated cells and reduced MyoD and myogenin activity at both proliferative and commitment stages. Otherwise, IL-1β increased myogenin activity only in committed cells. Our data reveal a key role of IL-6 and COX-2-derived PGs in IL-1β and TNF-α-induced myoblast proliferation and support the link between TNF-α and IL-6 and the activation of MRFs. We concluded that IL-1β and TNF-α induce similar effects at the initial stages of muscle regeneration but found critical differences between their effects with the progression of the process, bringing new insights into inflammatory signalling in skeletal muscle regeneration.

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 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 The Role of Metabolic Remodeling in Macrophage Polarization and Its Effect on Skeletal Muscle Regeneration

2019 ◽  
Vol 30 (12) ◽  
pp. 1553-1598 ◽  
Author(s):  
Francesca De Santa ◽  
Laura Vitiello ◽  
Alessio Torcinaro ◽  
Elisabetta Ferraro
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Macrophage Polarization ◽  
Skeletal Muscle Regeneration ◽  
Metabolic Remodeling

The COX-2 pathway regulates growth of atrophied muscle via multiple mechanisms

2006 ◽  
Vol 290 (6) ◽  
pp. C1651-C1659 ◽  
Author(s):  
Brenda A. Bondesen ◽  
Stephen T. Mills ◽  
Grace K. Pavlath
Keyword(s):  
Muscle Mass ◽  
Muscle Regeneration ◽  
Muscle Growth ◽  
Cell Activity ◽  
Hindlimb Suspension ◽  
Normal Muscle ◽  
Cox 2 ◽  
Proliferation In Vitro

Loss of muscle mass occurs with disease, injury, aging, and inactivity. Restoration of normal muscle mass depends on myofiber growth, the regulation of which is incompletely understood. Cyclooxygenase (COX)-2 is one of two isoforms of COX that catalyzes the synthesis of prostaglandins, paracrine hormones that regulate diverse physiological and pathophysiological processes. Previously, we demonstrated that the COX-2 pathway regulates early stages of myofiber growth during muscle regeneration. However, whether the COX-2 pathway plays a common role in adult myofiber growth or functions specifically during muscle regeneration is unknown. Therefore, we examined the role of COX-2 during myofiber growth following atrophy in mice. Muscle atrophy was induced by hindlimb suspension (HS) for 2 wk, followed by a reloading period, during which mice were treated with either the COX-2-selective inhibitor SC-236 (6 mg·kg−1·day−1) or vehicle. COX-2 protein was expressed and SC-236 attenuated myofiber growth during reloading in both soleus and plantaris muscles. Attenuated myofiber growth in the soleus was associated with both decreased myonuclear addition and decreased inflammation, whereas neither of these processes mediated the effects of SC-236 on plantaris growth. In addition, COX-2−/− satellite cells exhibited impaired activation/proliferation in vitro, suggesting direct regulation of muscle cell activity by COX-2. Together, these data suggest that the COX-2 pathway plays a common regulatory role during various types of muscle growth via multiple mechanisms.

The Anti-Inflammatory Potential of Mimosa caesalpiniifolia Following Experimental Colitis: Role of COX-2 and TNF-Alpha Expression

Drug Research ◽  
2017 ◽  
Vol 68 (04) ◽  
pp. 196-204 ◽  
Author(s):  
Marcelo Silva ◽  
Wagner Vilegas ◽  
Marcelo da Silva ◽  
Ana Paiotti ◽  
Mauricio Pastrelo ◽  
...  
Keyword(s):  
Protective Action ◽  
Experimental Colitis ◽  
Distal Colon ◽  
Tnf Alpha ◽  
High Dose ◽  
Dependent Manner ◽  
Hydroalcoholic Extract ◽  
Tnf Α ◽  
Cox 2

AbstractThe aim of this study was to evaluate the preventive and/or protective action of Mimosa caesalpiniifolia (M. caesalpiniifolia) following experimental colitis in rats. The rats were randomized into ten groups (n=10 per group), as follows: G1 – Sham group:; G2 – TNBS group; G3, G4 –colitis and treated with hydroalcoholic extract of M. caesalpiniifolia 250 mg/kg/day after and before/after inducing colitis, respectively; G5, G6 – colitis and treated with hydroalcoholic extract of M. caesalpiniifolia at 125 mg/kg/day after and before/after inducing colitis respectively; G7,G8 – colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively; G9,G10 – colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively. Rats treated with hydroalcoholic extract of M. caesalpiniifolia for both doses showed lower tissue damage in the distal colon. Ethylacetate fraction was effective at the highest dose only when administrated after inducing colitis. A downregulation of COX-2 was detected to rats suffering colitis and treated with M. caesalpiniifolia at high dose. On the other hand, TNF-alpha immunoexpression decreased in groups treated with M. caesalpiniifolia at low dose after inducing colitis. In summary, our results suggest that M. caesalpiniifolia attenuated the lesions of the colon, reduced inflammation, and modulates the expression of COX-2 and TNF-α during chronic colitis induced by TNBS when using for therapeutic purposes on a dose-dependent manner.

scholarly journals PEDF-derived peptide promotes skeletal muscle regeneration through its mitogenic effect on muscle progenitor cells

2015 ◽  
Vol 309 (3) ◽  
pp. C159-C168 ◽  
Author(s):  
Tsung-Chuan Ho ◽  
Yi-Pin Chiang ◽  
Chih-Kuang Chuang ◽  
Show-Li Chen ◽  
Jui-Wen Hsieh ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Proliferation ◽  
Cyclin D1 ◽  
Satellite Cell ◽  
Muscle Regeneration ◽  
Muscle Fibers ◽  
Skeletal Muscle Regeneration ◽  
Satellite Cell Proliferation

In response injury, intrinsic repair mechanisms are activated in skeletal muscle to replace the damaged muscle fibers with new muscle fibers. The regeneration process starts with the proliferation of satellite cells to give rise to myoblasts, which subsequently differentiate terminally into myofibers. Here, we investigated the promotion effect of pigment epithelial-derived factor (PEDF) on muscle regeneration. We report that PEDF and a synthetic PEDF-derived short peptide (PSP; residues Ser93-Leu112) induce satellite cell proliferation in vitro and promote muscle regeneration in vivo. Extensively, soleus muscle necrosis was induced in rats by bupivacaine, and an injectable alginate gel was used to release the PSP in the injured muscle. PSP delivery was found to stimulate satellite cell proliferation in damaged muscle and enhance the growth of regenerating myofibers, with complete regeneration of normal muscle mass by 2 wk. In cell culture, PEDF/PSP stimulated C2C12 myoblast proliferation, together with a rise in cyclin D1 expression. PEDF induced the phosphorylation of ERK1/2, Akt, and STAT3 in C2C12 myoblasts. Blocking the activity of ERK, Akt, or STAT3 with pharmacological inhibitors attenuated the effects of PEDF/PSP on the induction of C2C12 cell proliferation and cyclin D1 expression. Moreover, 5-bromo-2′-deoxyuridine pulse-labeling demonstrated that PEDF/PSP stimulated primary rat satellite cell proliferation in myofibers in vitro. In summary, we report for the first time that PSP is capable of promoting the regeneration of skeletal muscle. The signaling mechanism involves the ERK, AKT, and STAT3 pathways. These results show the potential utility of this PEDF peptide for muscle regeneration.

The Potential Role of Insulin-Like Growth Factors in Skeletal Muscle Regeneration

1996 ◽  
Vol 21 (4) ◽  
pp. 236-250 ◽  
Author(s):  
Jamie MacGregor ◽  
Wade S. Parkhouse
Keyword(s):  
Skeletal Muscle ◽  
Growth Hormone ◽  
Growth Factors ◽  
Muscle Regeneration ◽  
Potential Role ◽  
Tissue Growth ◽  
Skeletal Muscle Regeneration ◽  
Tissue Type ◽  
Insulin Like Growth Factors

The role of the insulin-like growth factors I and II (IGF-I and IGF-II), previously known as the somatomedins, in general growth and development of various tissues has been known for many years. Thought of exclusively as endocrine factors produced by the liver, and under the control of growth hormone, the somatomedins were known as the intermediaries by which growth hormone exerted its cellular effects during tissue growth and maturation. Eventually it was discovered that virtually every tissue type is capable of autocrine production of the IGFs, and their involvement in skeletal muscle tissue repair and regeneration became apparent. Recent advances in technology have allowed the characterisation of many of the different growth factors believed to play a role in muscle regeneration, and experimental manipulations of cells in culture have provided insight into the effects of the various growth factors on the myoblast. This paper explores the potential role of the IGFs in skeletal muscle regeneration. A critical role of IGF-II in terminal differentiation of proliferating muscle precurser cells following injury is proposed. Key words: growth factors, myogenesis, skeletal muscle regeneration

scholarly journals Chlorella vulgaris Improves the Regenerative Capacity of Young and Senescent Myoblasts and Promotes Muscle Regeneration

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Nurhazirah Zainul Azlan ◽  
Yasmin Anum Mohd Yusof ◽  
Ekram Alias ◽  
Suzana Makpol
Keyword(s):  
Chlorella Vulgaris ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Myoblast Differentiation ◽  
Regenerative Capacity ◽  
Maturation Index ◽  
Myoblast Cells ◽  
And Function ◽  
Pharmaceutical Uses

Sarcopenia is characterized by the loss of muscle mass, strength, and function with ageing. With increasing life expectancy, greater attention has been given to counteracting the effects of sarcopenia on the growing elderly population. Chlorella vulgaris, a microscopic, unicellular, green alga with the potential for various pharmaceutical uses, has been widely studied in this context. This study is aimed at determining the effects of C. vulgaris on promoting muscle regeneration by evaluating myoblast regenerative capacity in vitro. Human skeletal myoblast cells were cultured and underwent serial passaging into young and senescent phases and were then treated with C. vulgaris, followed by the induction of differentiation. The ability of C. vulgaris to promote myoblast differentiation was analysed through cellular morphology, real-time monitoring, cell proliferation, senescence-associated β-galactosidase (SA-β-gal) expression, myogenic differentiation, myogenin expression, and cell cycle profiling. The results obtained showed that senescent myoblasts exhibited an enlarged and flattened morphology, with increased SA-β-gal expression, reduced myogenic differentiation, decreased expression of myogenin, and an increased percentage of cells in the G0/G1 phase. Treatment with C. vulgaris resulted in decreased SA-β-gal expression and promotion of myogenic differentiation, as observed via an increased fusion index, maturation index, myotube size, and surface area and an increased percentage of cells that stained positive for myogenin. In conclusion, C. vulgaris improves the regenerative capacity of young and senescent myoblasts and promotes myoblast differentiation, indicating its potential to promote 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.

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