Morphological Evidence of Telocytes in Skeletal Muscle Interstitium of Exercised and Sedentary Rodents

Skeletal muscle atrophy, resulting from states of hypokinesis or immobilization, leads to morphological, metabolic, and functional changes within the muscle tissue, a large variety of which are supported by the stromal cells populating the interstitium. Telocytes represent a recently discovered population of stromal cells, which has been increasingly identified in several human organs and appears to participate in sustaining cross-talk, promoting regenerative mechanisms and supporting differentiation of local stem cell niche. The aim of this morphologic study was to investigate the presence of Telocytes in the tibialis anterior muscle of healthy rats undergoing an endurance training protocol for either 4 weeks or 16 weeks compared to sedentary rats. Histomorphometric analysis of muscle fibers diameter revealed muscle atrophy in sedentary rats. Telocytes were identified by double-positive immunofluorescence staining for CD34/CD117 and CD34/vimentin. The results showed that Telocytes were significantly reduced in sedentary rats at 16 weeks, while rats subjected to regular exercise maintained a stable Telocytes population after 16 weeks. Understanding of the relationship between Telocytes and exercise offers new chances in the field of regenerative medicine, suggesting possible triggers for Telocytes in sarcopenia and other musculoskeletal disorders, promoting adapted physical activity and rehabilitation programmes in clinical practice.

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miR-23a is decreased during muscle atrophy by a mechanism that includes calcineurin signaling and exosome-mediated export

AJP Cell Physiology ◽

10.1152/ajpcell.00266.2013 ◽

2014 ◽

Vol 306 (6) ◽

pp. C551-C558 ◽

Cited By ~ 74

Author(s):

Matthew B. Hudson ◽

Myra E. Woodworth-Hobbs ◽

Bin Zheng ◽

Jill A. Rahnert ◽

Mitsi A. Blount ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Atrophy ◽

Ring Finger ◽

Skeletal Muscle Atrophy ◽

C2c12 Myotubes ◽

Activated T Cells ◽

Streptozotocin Induced Diabetes ◽

The Media ◽

The Relationship ◽

Deficient Mice

Skeletal muscle atrophy is prevalent in chronic diseases, and microRNAs (miRs) may play a key role in the wasting process. miR-23a was previously shown to inhibit the expression of atrogin-1 and muscle RING-finger protein-1 (MuRF1) in muscle. It also was reported to be regulated by cytoplasmic nuclear factor of activated T cells 3 (NFATc3) in cardiomyocytes. The objective of this study was to determine if miR-23a is regulated during muscle atrophy and to evaluate the relationship between calcineurin (Cn)/NFAT signaling and miR-23a expression in skeletal muscle cells during atrophy. miR-23a was decreased in the gastrocnemius of rats with acute streptozotocin-induced diabetes, a condition known to increase atrogin-1 and MuRF1 expression and cause atrophy. Treatment of C2C12 myotubes with dexamethasone (Dex) for 48 h also reduced miR-23a as well as RCAN1.4 mRNA, which is transcriptionally regulated by NFAT. NFATc3 nuclear localization and the amount of miR-23a decreased rapidly within 1 h of Dex administration, suggesting a link between Cn signaling and miR-23a. The level of miR-23a was lower in primary myotubes from mice lacking the α- or β-isoform of the CnA catalytic subunit than wild-type mice. Dex did not further suppress miR-23a in myotubes from Cn-deficient mice. Overexpression of CnAβ in C2C12 myotubes prevented Dex-induced suppression of miR-23a. Finally, miR-23a was present in exosomes isolated from the media of C2C12 myotubes, and Dex increased its exosomal abundance. Dex did not alter the number of exosomes released into the media. We conclude that atrophy-inducing conditions downregulate miR-23a in muscle by mechanisms involving attenuated Cn/NFAT signaling and selective packaging into exosomes.

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Metronidazole Causes Skeletal Muscle Atrophy and Modulates Muscle Chronometabolism

International Journal of Molecular Sciences ◽

10.3390/ijms19082418 ◽

2018 ◽

Vol 19 (8) ◽

pp. 2418 ◽

Cited By ~ 11

Author(s):

Ravikumar Manickam ◽

Hui Oh ◽

Chek Tan ◽

Eeswari Paramalingam ◽

Walter Wahli

Keyword(s):

Skeletal Muscle ◽

Muscle Atrophy ◽

Metabolic Regulation ◽

Target Genes ◽

Clock Genes ◽

Tibialis Anterior Muscle ◽

Skeletal Muscle Atrophy ◽

Muscle Weight ◽

Expression Of Genes ◽

Specific Pathogen

Antibiotics lead to increased susceptibility to colonization by pathogenic organisms, with different effects on the host-microbiota relationship. Here, we show that metronidazole treatment of specific pathogen-free (SPF) mice results in a significant increase of the bacterial phylum Proteobacteria in fecal pellets. Furthermore, metronidazole in SPF mice decreases hind limb muscle weight and results in smaller fibers in the tibialis anterior muscle. In the gastrocnemius muscle, metronidazole causes upregulation of Hdac4, myogenin, MuRF1, and atrogin1, which are implicated in skeletal muscle neurogenic atrophy. Metronidazole in SPF mice also upregulates skeletal muscle FoxO3, described as involved in apoptosis and muscle regeneration. Of note, alteration of the gut microbiota results in increased expression of the muscle core clock and effector genes Cry2, Ror-β, and E4BP4. PPARγ and one of its important target genes, adiponectin, are also upregulated by metronidazole. Metronidazole in germ-free (GF) mice increases the expression of other core clock genes, such as Bmal1 and Per2, as well as the metabolic regulators FoxO1 and Pdk4, suggesting a microbiota-independent pharmacologic effect. In conclusion, metronidazole in SPF mice results in skeletal muscle atrophy and changes the expression of genes involved in the muscle peripheral circadian rhythm machinery and metabolic regulation.

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UBE2E1 Is Preferentially Expressed in the Cytoplasm of Slow-Twitch Fibers and Protects Skeletal Muscles from Exacerbated Atrophy upon Dexamethasone Treatment

Cells ◽

10.3390/cells7110214 ◽

2018 ◽

Vol 7 (11) ◽

pp. 214 ◽

Cited By ~ 2

Author(s):

Cécile Polge ◽

Julien Aniort ◽

Andrea Armani ◽

Agnès Claustre ◽

Cécile Coudy-Gandilhon ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Muscle Atrophy ◽

Tibialis Anterior Muscle ◽

Ubiquitin Proteasome System ◽

Skeletal Muscle Atrophy ◽

C2c12 Myotubes ◽

Type I ◽

Dexamethasone Treatment ◽

Sarcomeric Protein

Skeletal muscle mass is reduced during many diseases or physiological situations (disuse, aging), which results in decreased strength and increased mortality. Muscle mass is mainly controlled by the ubiquitin-proteasome system (UPS), involving hundreds of ubiquitinating enzymes (E2s and E3s) that target their dedicated substrates for subsequent degradation. We recently demonstrated that MuRF1, an E3 ubiquitin ligase known to bind to sarcomeric proteins (telethonin, α-actin, myosins) during catabolic situations, interacts with 5 different E2 enzymes and that these E2-MuRF1 couples are able to target telethonin, a small sarcomeric protein, for degradation. Amongst the E2s interacting with MuRF1, E2E1 was peculiar as the presence of the substrate was necessary for optimal MuRF1-E2E1 interaction. In this work, we focused on the putative role of E2E1 during skeletal muscle atrophy. We found that E2E1 expression was restricted to type I and type IIA muscle fibers and was not detectable in type IIB fibers. This strongly suggests that E2E1 targets are fiber-specific and may be strongly linked to the contractile and metabolic properties of the skeletal muscle. However, E2E1 knockdown was not sufficient for preserving the protein content in C2C12 myotubes subjected to a catabolic state (dexamethasone treatment), suggesting that E2E1 is not involved in the development of muscle atrophy. By contrast, E2E1 knockdown aggravated the atrophying process in both catabolic C2C12 myotubes and the Tibialis anterior muscle of mice, suggesting that E2E1 has a protective effect on muscle mass.

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Oleamide rescues tibialis anterior muscle atrophy of mice housed in small cages

British Journal Of Nutrition ◽

10.1017/s0007114520004304 ◽

2020 ◽

pp. 1-11

Author(s):

Yasuyuki Kobayashi ◽

Natsumi Watanabe ◽

Tomoya Kitakaze ◽

Keiichiro Sugimoto ◽

Takeshi Izawa ◽

...

Keyword(s):

Skeletal Muscle ◽

Plasma Concentration ◽

Muscle Atrophy ◽

Tibialis Anterior ◽

Metabolic Diseases ◽

Tibialis Anterior Muscle ◽

Skeletal Muscle Atrophy ◽

C2c12 Myotubes ◽

Sequestosome 1 ◽

Increased Risk

Abstract Skeletal muscle atrophy causes decreased physical activity and increased risk of metabolic diseases. We investigated the effects of oleamide (cis-9,10-octadecanamide) treatment on skeletal muscle health. The plasma concentration of endogenous oleamide was approximately 30 nm in male ddY mice under normal physiological conditions. When the stable isotope-labelled oleamide was orally administered to male ddY mice (50 mg/kg), the plasma concentration of exogenous oleamide reached approximately 170 nm after 1 h. Male ddY mice were housed in small cages (one-sixth of normal size) to enforce sedentary behaviour and orally administered oleamide (50 mg/kg per d) for 4 weeks. Housing in small cages decreased tibialis anterior (TA) muscle mass and the cross-sectional area of the myofibres in TA muscle. Dietary oleamide alleviated the decreases in TA muscle and resulted in plasma oleamide concentration of approximately 120 nm in mice housed in small cages. Housing in small cages had no influence on the phosphorylation levels of Akt serine/threonine kinase (Akt), mechanistic target of rapamycin (mTOR) and ribosomal protein S6 kinase (p70S6K) in TA muscle; nevertheless, oleamide increased the phosphorylation levels of the proteins. Housing in small cages increased the expression of microtubule-associated protein 1 light chain 3 (LC3)-II and sequestosome 1 (p62), but not LC3-I, in TA muscle, and oleamide reduced LC3-I, LC3-II and p62 expression levels. In C2C12 myotubes, oleamide increased myotube diameter at ≥100 nm. Furthermore, the mTOR inhibitor, Torin 1, suppressed oleamide-induced increases in myotube diameter and protein synthesis. These results indicate that dietary oleamide rescued TA muscle atrophy in mice housed in small cages, possibly by activating the phosphoinositide 3-kinase/Akt/mTOR signalling pathway and restoring autophagy flux.

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Swim training affects Akt signaling and ameliorates loss of skeletal muscle mass in a mouse model of amyotrophic lateral sclerosis

Scientific Reports ◽

10.1038/s41598-021-00319-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Karol Cieminski ◽

Damian Jozef Flis ◽

Katarzyna Dzik ◽

Jan Jacek Kaczor ◽

Emilia Czyrko ◽

...

Keyword(s):

Skeletal Muscle ◽

Signaling Pathway ◽

Muscle Mass ◽

Muscle Atrophy ◽

Skeletal Muscle Mass ◽

Tibialis Anterior Muscle ◽

Akt Signaling ◽

The Body ◽

Skeletal Muscle Atrophy ◽

Akt Signaling Pathway

AbstractWe tested the hypothesis that swim training reverses the impairment of Akt/FOXO3a signaling, ameliorating muscle atrophy in ALS mice. Transgenic male mice B6SJL-Tg (SOD1G93A) 1Gur/J were used as the ALS model (n = 35), with wild-type B6SJL (WT) mice as controls (n = 7). ALS mice were analyzed before ALS onset, at ALS onset, and at terminal ALS. Levels of insulin/Akt signaling pathway proteins were determined, and the body and tibialis anterior muscle mass and plasma creatine kinase. Significantly increased levels of FOXO3a in ALS groups (from about 13 to 21-fold) compared to WT mice were observed. MuRF1 levels in the ONSET untrained group (12.0 ± 1.7 AU) were significantly higher than in WT mice (1.12 ± 0.2 AU) and in the BEFORE ALS group (3.7 ± 0.9 AU). This was associated with body mass and skeletal muscle mass reduction. Swim training significantly ameliorated the reduction of skeletal muscle mass in both TERMINAL groups (p < 0.001) and partially reversed changes in the levels of Akt signaling pathway proteins. These findings shed light on the swimming-induced attenuation of skeletal muscle atrophy in ALS with possible practical implications for anti-cachexia approaches.

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