Modulation of Caspase Activity Regulates Skeletal Muscle Regeneration and Function in Response to Vasopressin and Tumor Necrosis Factor

Skeletal muscle atrophy occurs during disuse and aging, or as a consequence of chronic diseases such as cancer and diabetes. It is characterized by progressive loss of muscle tissue due to hypotrophic changes, degeneration, and an inability of the regeneration machinery to replace damaged myofibers. Tumor necrosis factor (TNF) is a proinflammatory cytokine known to mediate muscle atrophy in many chronic diseases and to inhibit skeletal muscle regeneration. In this study, we investigated the role of Arg-vasopressin-(AVP-)dependent pathways in muscles in which atrophy was induced by local overexpression of TNF. AVP is a potent myogenesis-promoting factor and is able to enhance skeletal muscle regeneration by stimulating Ca2+/calmodulin-dependent kinase and calcineurin signaling. We performed morphological and molecular analyses and demonstrated that local over-expression of the AVP receptor V1a enhances regeneration of atrophic muscle. By upregulating the regeneration/differentiation markers, modulating the inflammatory response, and attenuating fibrogenesis, the stimulation of AVP-dependent pathways creates a favourable environment for efficient and sustained muscle regeneration and repair even in the presence of elevated levels of TNF. This study highlights a novelin vivorole for AVP-dependent pathways, which may represent an interesting strategy to counteract muscle decline in aging or in muscular pathologies.

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The Role of Tumor Necrosis Factor-alpha (TNF-α) in Skeletal Muscle Regeneration

Journal of Histochemistry & Cytochemistry ◽

10.1177/002215540104900807 ◽

2001 ◽

Vol 49 (8) ◽

pp. 989-1001 ◽

Cited By ~ 95

Author(s):

Rachel A. Collins ◽

Miranda D. Grounds

Keyword(s):

Skeletal Muscle ◽

Tumor Necrosis Factor ◽

Muscle Regeneration ◽

Tumor Necrosis ◽

Necrosis Factor Alpha ◽

Tissue Sections ◽

Tnf Α ◽

Factor Alpha ◽

Necrosis Factor

The role of tumor necrosis factor-alpha (TNF-α), an important mediator of the inflammatory response after injury, was investigated in regenerating skeletal muscle. The pattern of expression of TNF-α during muscle regeneration was examined by immunohistochemistry in tissue sections of crush-injured or transplanted muscle autografts and in primary cultures of adult skeletal muscle. TNF-α was highly expressed in injured myofibers, inflammatory cells, endothelial cells, fibroblasts, and mast cells. Myoblasts and myotubes also expressed TNF-α in primary muscle cultures and tissue sections. The essential role of TNF-α and its homologue lymphotoxin-alpha (LT-α) during muscle regeneration was assessed by basic histology in TNF-α(–) and TNF-α(-/-)/LT-α(-/-) mice. No difference was apparent in the onset or pattern of muscle regeneration (i.e., inflammatory response, activation and fusion of myoblasts) between the two strains of null mice or between nulls and normal control mice. However, both strains of null mice appeared more prone to bystander damage of host muscle and regeneration distant from the site of injury/transplantation. Although expression of TNF-α may play an important role in muscle regeneration, the studies in the null mice show that redundancy within the cytokine system (or some other response) can effectively compensate for the absence of TNF-α in vivo. (J Histochem Cytochem 49:989–1001, 2001)

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Review for "Tumor necrosis factor receptor family co‐stimulation increases regulatory T cell activation and function via NF‐κB"

10.1002/eji.201948393/v1/review1 ◽

2019 ◽

Keyword(s):

T Cell ◽

Tumor Necrosis Factor ◽

T Cell Activation ◽

Regulatory T Cell ◽

Tumor Necrosis ◽

Cell Activation ◽

Tumor Necrosis Factor Receptor ◽

And Function ◽

Necrosis Factor ◽

Receptor Family

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Treadmill exercise training could attenuate the upregulation of Interleukin-1 beta and tumor necrosis factor alpha in the skeletal muscle of mouse model of chronic/progressive Parkinson disease

Neurorehabilitation ◽

10.3233/nre-182492 ◽

2019 ◽

Vol 43 (4) ◽

pp. 501-507 ◽

Cited By ~ 1

Author(s):

Muhammed D. Al-Jarrah ◽

Nour S. Erekat

Keyword(s):

Skeletal Muscle ◽

Tumor Necrosis Factor ◽

Exercise Training ◽

Tumor Necrosis ◽

Treadmill Exercise ◽

Interleukin 1 ◽

Interleukin 1 Beta ◽

Necrosis Factor Alpha ◽

Factor Alpha ◽

Necrosis Factor

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Human granulocyte-monocyte colony-stimulating factor and interleukin 3 stimulate monocyte cytotoxicity through a tumor necrosis factor- dependent mechanism

Blood ◽

10.1182/blood.v71.3.672.bloodjournal713672 ◽

1988 ◽

Vol 71 (3) ◽

pp. 672-676

Author(s):

SA Cannistra ◽

E Vellenga ◽

P Groshek ◽

A Rambaldi ◽

JD Griffin

Keyword(s):

Tumor Necrosis Factor ◽

Messenger Rna ◽

Tumor Necrosis ◽

Tumoricidal Activity ◽

Interleukin 3 ◽

Gm Csf ◽

And Function ◽

Monocyte Cytotoxicity ◽

Necrosis Factor ◽

Dependent Mechanism

Human colony-stimulating factors (CSF) exert multiple effects on the proliferation, differentiation, and function of myeloid lineage cells. In this study, the effects of three recombinant human CSFs (granulocyte- monocyte CSF [GM-CSF], interleukin 3 [IL-3], and granulocyte CSF [G- CSF]) on antibody-independent monocyte tumoricidal activity were investigated by using WEHI 164 fibrosarcoma cells as monocyte-sensitive targets. None of the CSFs directly induced monocyte cytotoxicity, although both GM-CSF and IL-3 were found to significantly enhance monocyte killing in response to a second stimulatory event (endotoxin). No effect was seen with G-CSF. Antitumor necrosis factor antibody completely abolished CSF-enhanced monocyte cytotoxicity, which suggests that this effect was mediated through increased release of tumor necrosis factor (TNF). As previously shown for GM-CSF, IL-3 was found to induce cytoplasmic accumulation of TNF messenger RNA (mRNA) after 18 hours of exposure. These results suggest that GM-CSF and IL-3 may stimulate monocyte killing indirectly by enhancing expression of TNF mRNA, thereby leading to augmented TNF protein secretion in response to a second activation signal.

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Signaling and Function of Death Receptors of the Tumor Necrosis Factor Receptor Superfamily

Encyclopedia of Cell Biology ◽

10.1016/b978-0-12-394447-4.30011-6 ◽

2016 ◽

pp. 67-75

Author(s):

S. Skeldal ◽

E.J. Coulson

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Receptor ◽

Death Receptors ◽

And Function ◽

Necrosis Factor

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IL-4 and SDF-1 Increase Adipose Tissue-Derived Stromal Cell Ability to Improve Rat Skeletal Muscle Regeneration

International Journal of Molecular Sciences ◽

10.3390/ijms21093302 ◽

2020 ◽

Vol 21 (9) ◽

pp. 3302

Author(s):

Małgorzata Zimowska ◽

Karolina Archacka ◽

Edyta Brzoska ◽

Joanna Bem ◽

Areta M. Czerwinska ◽

...

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Muscle Regeneration ◽

Structure And Function ◽

Skeletal Muscle Regeneration ◽

Stem Cell Markers ◽

Myogenic Factors ◽

And Function

Skeletal muscle regeneration depends on the satellite cells, which, in response to injury, activate, proliferate, and reconstruct damaged tissue. However, under certain conditions, such as large injuries or myopathies, these cells might not sufficiently support repair. Thus, other cell populations, among them adipose tissue-derived stromal cells (ADSCs), are tested as a tool to improve regeneration. Importantly, the pro-regenerative action of such cells could be improved by various factors. In the current study, we tested whether IL-4 and SDF-1 could improve the ability of ADSCs to support the regeneration of rat skeletal muscles. We compared their effect at properly regenerating fast-twitch EDL and poorly regenerating slow-twitch soleus. To this end, ADSCs subjected to IL-4 and SDF-1 were analyzed in vitro and also in vivo after their transplantation into injured muscles. We tested their proliferation rate, migration, expression of stem cell markers and myogenic factors, their ability to fuse with myoblasts, as well as their impact on the mass, structure and function of regenerating muscles. As a result, we showed that cytokine-pretreated ADSCs had a beneficial effect in the regeneration process. Their presence resulted in improved muscle structure and function, as well as decreased fibrosis development and a modulated immune response.

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