Induction and maintenance of increased VEGF protein by chronic motor nerve stimulation in skeletal muscle

1998 ◽  
Vol 274 (3) ◽  
pp. H860-H867 ◽  
Author(s):  
Brian H. Annex ◽  
Carol E. Torgan ◽  
Pengnian Lin ◽  
Doris A. Taylor ◽  
Michael A. Thompson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Nerve Stimulation ◽  
Skeletal Muscles ◽  
Motor Nerve ◽  
Capillary Density ◽  
Endothelial Cell Proliferation ◽  
Vascular Density ◽  
Oxidative Phenotype ◽  
Vegf Protein

Vascular endothelial growth factor (VEGF) causes endothelial cell proliferation in vitro and angiogenesis in vivo. Glycolytic skeletal muscles have a lower capillary density than oxidative muscles but can increase their capillary density and convert to a more oxidative phenotype when subject to chronic motor nerve stimulation (CMNS). We used Western analysis and immunohistochemical techniques to examine VEGF protein in a rabbit CMNS model of glycolytic skeletal muscle and in muscles with innate glycolytic versus oxidative phenotypes. VEGF protein per gram of total protein was increased in stimulated vs. control muscles 2.9 ± 1.0, 3.6 ± 1.3, 3.1 ± 0.5, 4.4 ± 1.6, and 2.7 ± 0.3 times after 3 ( n = 4), 5 ( n = 2), 10 ( n = 3), 21 ( n = 3), and 56 ( n = 2) days, respectively. VEGF protein was increased 3.1 ± 0.5 times ( P < 0.005) before (3, 5, and 10 days) and remained elevated 3.7 ± 1.0 times ( P < 0.05) after (21 and 56 days) the transition to an oxidative phenotype. By immunohistochemistry, VEGF protein was found primarily in the matrix between stimulated muscle fibers but not in the myocytes. In addition, VEGF protein was consistently lower in innate glycolytic compared with oxidative muscles. These findings suggest that VEGF plays a role in the alteration and maintenance of vascular density in mammalian skeletal muscles.

scholarly journals Bioengineered in vitro skeletal muscles as new tools for muscular dystrophies preclinical studies

2021 ◽  
Vol 12 ◽  
pp. 204173142098133
Author(s):  
Juan M. Fernández-Costa ◽  
Xiomara Fernández-Garibay ◽  
Ferran Velasco-Mallorquí ◽  
Javier Ramón-Azcón
Keyword(s):  
Skeletal Muscle ◽  
Tissue Engineering ◽  
Electrical Stimulation ◽  
Skeletal Muscles ◽  
Screening Tools ◽  
Muscular Dystrophies ◽  
Preclinical Studies ◽  
Technological Advances ◽  
Topographical Cues

Muscular dystrophies are a group of highly disabling disorders that share degenerative muscle weakness and wasting as common symptoms. To date, there is not an effective cure for these diseases. In the last years, bioengineered tissues have emerged as powerful tools for preclinical studies. In this review, we summarize the recent technological advances in skeletal muscle tissue engineering. We identify several ground-breaking techniques to fabricate in vitro bioartificial muscles. Accumulating evidence shows that scaffold-based tissue engineering provides topographical cues that enhance the viability and maturation of skeletal muscle. Functional bioartificial muscles have been developed using human myoblasts. These tissues accurately responded to electrical and biological stimulation. Moreover, advanced drug screening tools can be fabricated integrating these tissues in electrical stimulation platforms. However, more work introducing patient-derived cells and integrating these tissues in microdevices is needed to promote the clinical translation of bioengineered skeletal muscle as preclinical tools for muscular dystrophies.

scholarly journals Tenogenic Contribution to Skeletal Muscle Regeneration: The Secretome of Scleraxis Overexpressing Mesenchymal Stem Cells Enhances Myogenic Differentiation In Vitro

2020 ◽  
Vol 21 (6) ◽  
pp. 1965
Author(s):  
Maximilian Strenzke ◽  
Paolo Alberton ◽  
Attila Aszodi ◽  
Denitsa Docheva ◽  
Elisabeth Haas ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Skeletal Muscles ◽  
Myogenic Differentiation ◽  
Muscular Contraction ◽  
Myoblast Fusion ◽  
Skeletal Muscle Regeneration ◽  
Potential Candidate ◽  
Musculoskeletal Tissue

Integrity of the musculoskeletal system is essential for the transfer of muscular contraction force to the associated bones. Tendons and skeletal muscles intertwine, but on a cellular level, the myotendinous junctions (MTJs) display a sharp transition zone with a highly specific molecular adaption. The function of MTJs could go beyond a mere structural role and might include homeostasis of this musculoskeletal tissue compound, thus also being involved in skeletal muscle regeneration. Repair processes recapitulate several developmental mechanisms, and as myotendinous interaction does occur already during development, MTJs could likewise contribute to muscle regeneration. Recent studies identified tendon-related, scleraxis-expressing cells that reside in close proximity to the MTJs and the muscle belly. As the muscle-specific function of these scleraxis positive cells is unknown, we compared the influence of two immortalized mesenchymal stem cell (MSC) lines—differing only by the overexpression of scleraxis—on myoblasts morphology, metabolism, migration, fusion, and alignment. Our results revealed a significant increase in myoblast fusion and metabolic activity when exposed to the secretome derived from scleraxis-overexpressing MSCs. However, we found no significant changes in myoblast migration and myofiber alignment. Further analysis of differentially expressed genes between native MSCs and scleraxis-overexpressing MSCs by RNA sequencing unraveled potential candidate genes, i.e., extracellular matrix (ECM) proteins, transmembrane receptors, or proteases that might enhance myoblast fusion. Our results suggest that musculotendinous interaction is essential for the development and healing of skeletal muscles.

Structural and functional remodeling of skeletal muscle microvasculature is induced by simulated microgravity

2000 ◽  
Vol 278 (6) ◽  
pp. H1866-H1873 ◽  
Author(s):  
Michael D. Delp ◽  
Patrick N. Colleran ◽  
M. Keith Wilkerson ◽  
Matthew R. McCurdy ◽  
Judy Muller-Delp
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Skeletal Muscles ◽  
Gastrocnemius Muscle ◽  
Fluid Pressure ◽  
Hindlimb Unloading ◽  
Cross Sectional ◽  
Luminal Diameter ◽  
Structural Remodeling

Hindlimb unloading of rats results in a diminished ability of skeletal muscle arterioles to constrict in vitro and elevate vascular resistance in vivo. The purpose of the present study was to determine whether alterations in the mechanical environment (i.e., reduced fluid pressure and blood flow) of the vasculature in hindlimb skeletal muscles from 2-wk hindlimb-unloaded (HU) rats induces a structural remodeling of arterial microvessels that may account for these observations. Transverse cross sections were used to determine media cross-sectional area (CSA), wall thickness, outer perimeter, number of media nuclei, and vessel luminal diameter of feed arteries and first-order (1A) arterioles from soleus and the superficial portion of gastrocnemius muscles. Endothelium-dependent dilation (ACh) was also determined. Media CSA of resistance arteries was diminished by hindlimb unloading as a result of decreased media thickness (gastrocnemius muscle) or reduced vessel diameter (soleus muscle). ACh-induced dilation was diminished by 2 wk of hindlimb unloading in soleus 1A arterioles, but not in gastrocnemius 1A arterioles. These results indicate that structural remodeling and functional adaptations of the arterial microvasculature occur in skeletal muscles of the HU rat; the data suggest that these alterations may be induced by reductions in transmural pressure (gastrocnemius muscle) and wall shear stress (soleus muscle).

Expression of steroidogenic enzymes and synthesis of sex steroid hormones from DHEA in skeletal muscle of rats

2007 ◽  
Vol 292 (2) ◽  
pp. E577-E584 ◽  
Author(s):  
Katsuji Aizawa ◽  
Motoyuki Iemitsu ◽  
Seiji Maeda ◽  
Subrina Jesmin ◽  
Takeshi Otsuki ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Steroid Hormones ◽  
Skeletal Muscles ◽  
Muscle Cells ◽  
Sex Steroid Hormones ◽  
Sex Steroid ◽  
Dependent Manner ◽  
Steroidogenic Enzymes

The functional importance of sex steroid hormones (testosterone and estrogens), derived from extragonadal tissues, has recently gained significant appreciation. Circulating dehydroepiandrosterone (DHEA) is peripherally taken up and converted to testosterone by 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD, and testosterone in turn is irreversibly converted to estrogens by aromatase cytochrome P-450 (P450arom). Although sex steroid hormones have been implicated in skeletal muscle regulation and adaptation, it is unclear whether skeletal muscles have a local steroidogenic enzymatic machinery capable of metabolizing circulating DHEA. Thus, here, we investigate whether the three key steroidogenic enzymes (3β-HSD, 17β-HSD, and P450arom) are present in the skeletal muscle and are capable of generating sex steroid hormones. Consistent with our hypothesis, the present study demonstrates mRNA and protein expression of these enzymes in the skeletal muscle cells of rats both in vivo and in culture (in vitro). Importantly, we also show an intracellular formation of testosterone and estradiol from DHEA or testosterone in cultured muscle cells in a dose-dependent manner. These findings are novel and important in that they provide the first evidence showing that skeletal muscles are capable of locally synthesizing sex steroid hormones from circulating DHEA or testosterone.

scholarly journals In Vivo Activation of STAT3 Signaling in Satellite Cells and Myofibers in Regenerating Rat Skeletal Muscles

2002 ◽  
Vol 50 (12) ◽  
pp. 1579-1589 ◽  
Author(s):  
Katsuya Kami ◽  
Emiko Senba
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Intracellular Signaling ◽  
Skeletal Muscles ◽  
Early Stage ◽  
Skeletal Muscle Regeneration ◽  
Stat3 Signaling

Although growth factors and cytokines play critical roles in skeletal muscle regeneration, intracellular signaling molecules that are activated by these factors in regenerating muscles have been not elucidated. Several lines of evidence suggest that leukemia inhibitory factor (LIF) is an important cytokine for the proliferation and survival of myoblasts in vitro and acceleration of skeletal muscle regeneration. To elucidate the role of LIF signaling in regenerative responses of skeletal muscles, we examined the spatial and temporal activation patterns of an LIF-associated signaling molecule, the signal transducer and activator transcription 3 (STAT3) proteins in regenerating rat skeletal muscles induced by crush injury. At the early stage of regeneration, activated STAT3 proteins were first detected in the nuclei of activated satellite cells and then continued to be activated in proliferating myoblasts expressing both PCNA and MyoD proteins. When muscle regeneration progressed, STAT3 signaling was no longer activated in differentiated myoblasts and myotubes. In addition, activation of STAT3 was also detected in myonuclei within intact sarcolemmas of surviving myofibers that did not show signs of necrosis. These findings suggest that activation of STAT3 signaling is an important molecular event that induces the successful regeneration of injured skeletal muscles.

Glutamine Metabolism in Skeletal Muscle of Glucocorticoid-Treated Rats

1990 ◽  
Vol 79 (2) ◽  
pp. 139-147 ◽  
Author(s):  
M. Salleh M. Ardawi ◽  
Yasir S. Jamal
Keyword(s):  
Skeletal Muscle ◽  
Exchange Rates ◽  
Skeletal Muscles ◽  
Plasma Concentrations ◽  
Maximal Activity ◽  
Glutamine Metabolism ◽  
Dexamethasone Treatment ◽  
Concentration Difference

1. The effect of dexamethasone (30 μg day−-1 100 g−-1 body weight) on the regulation of glutamine metabolism was studied in skeletal muscles of rats after 9 days of treatment. 2. Dexamethasone resulted in negative nitrogen balance, and produced increases in the plasma concentrations of alanine (23.4%) and insulin (158%) but a decrease in the plasma concentration of glutamine (28.7%). 3. Dexamethasone treatment increased the rate of glutamine production in muscle, skin and adipose tissue preparations, with muscle production accounting for over 90% of total glutamine produced by the hindlimb. 4. Blood flow and arteriovenous concentration difference measurements across the hindlimb showed an increase in the net exchange rates of glutamine (25.3%) and alanine (90.5%) in dexamethasone-treated rats compared with corresponding controls. 5. Dexamethasone treatment produced significant decreases in the concentrations of skeletal muscle glutamine (51.8%) and 2-oxoglutarate (50.8%). The concentrations of alanine (16.2%), pyruvate (45.9%), ammonia (43.3%) and inosine 5′-phosphate (141.8%) were increased. 6. The maximal activity of glutamine synthetase was increased (21–34%), but there was no change in that of glutaminase, in muscles of dexamethasone-treated rats. 7. It is concluded that glucocorticoid administration enhances the rates of release of both glutamine and alanine from skeletal muscle of rats (both in vitro and in vivo). This may be due to changes in efflux and/or increased intracellular formation of glutamine and alanine.

The in vitro effect of corticosterone on insulin binding and glucose metabolism in mouse skeletal muscles

1985 ◽  
Vol 63 (9) ◽  
pp. 1133-1138 ◽  
Author(s):  
M. H. Tan ◽  
A. Bonen
Keyword(s):  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Extensor Digitorum Longus ◽  
Insulin Binding ◽  
In Vivo Model ◽  
In Vitro System ◽  
Vitro Effect ◽  
Contralateral Muscle

We studied the in vitro effect of corticosterone on insulin binding, uptake of 2-deoxy-D-glucose, glycolysis, and glycogenesis in the soleus and extensor digitorum longus (EDL) of Swiss–Webster mice. In each experiment, one muscle (soleus/EDL) was incubated with corticosterone (0.1, 1, 50, and 100 μg/mL) and the respective contralateral muscle was incubated without corticosterone, but at the same insulin and pH levels. Corticosterone did not affect insulin binding in both muscles. However, corticosterone decreased the uptake of 2-deoxy-D-glucose and the rate of glycolysis and glycogenesis in both muscles when the dose was pharmacologic (50 and 100 μg/mL), but not when it was physiologic (0.1 and 1 μg/mL). For glycolysis and glycogenesis, the suppression was greater in the EDL when compared with the soleus. This suppression was seen in both basal and insulin-stimulated conditions. In this in vitro system, where the experimental muscle is not exposed to prior hyperinsulinemia as in the in vivo model, corticosterone, at pharmacologic doses, affects postreceptor events without altering the insulin binding in the skeletal muscle.

Capillary supply of skeletal muscles from acclimatized white-footed mice Peromyscus

1981 ◽  
Vol 241 (5) ◽  
pp. R357-R361
Author(s):  
S. J. Wickler
Keyword(s):  
Skeletal Muscle ◽  
Heat Production ◽  
Skeletal Muscles ◽  
Capillary Density ◽  
Area Index ◽  
Fiber Area ◽  
Hindlimb Muscles ◽  
The Mean ◽  
Thermogenic Capacity ◽  
Muscle Capillaries

Winter-acclimatized white-footed mice (Peromyscus leucopus) can increase their aerobic heat production under cold stress by 70%. The possibility that changes in microvascular supply might account, in part, for some of this increased thermogenic capacity was examined in one of the primary thermogenic tissues, skeletal muscle. Capillaries were stained histochemically in four hindlimb muscles of freshly captured Peromyscus in summer and winter. Capillary density, mean fiber area, and mean capillaries in contact per muscle fiber were obtained from the soleus, plantaris, gastrocnemius, and semitendinosus. If results from all individual muscles are combined, mean fiber area is significantly smaller (8%) and mean capillary density is significantly greater (40%) in winter muscles. The mean number of capillaries in contact is not different, but the mean ratio of capillaries in contact per mean fiber area (index of potential perfusion) is significantly greater (25%) in winter muscles.

A comparison of the antidotal effects of three oximes against an organophosphate on chick skeletal muscle

2021 ◽  
Keyword(s):  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Motor Nerve ◽  
Toxic Effects ◽  
Hi 6 ◽  
Msec Duration ◽  
Organophosphorus Poisoning ◽  
Pre Treatment ◽  
Nerve Muscle ◽  
Time Of Administration

Background: One of the most toxic effects of organophosphorus poisoning (OP) is the paralysis of skeletal muscles. The oximes are a group of available antidotes. This study investigated the effects of different concentrations of paraoxon on the function of skeletal muscle and reversal or prevention of these effects by three different oximes (i.e., pralidoxime, obidoxime, and HI-6). Materials and Methods: This study was conducted based on the chicken biventer cervices (CBC) nerve-muscle preparation and the use of twitch tension recording technique. The twitches of the CBC were evoked by stimulating the motor nerve at 0.1 Hz with pulses of 0.2 msec duration and a voltage greater than that required to produce the maximum response. Moreover, twitches and contractures were recorded isotonically using Grass Biosystems. Results: Paraoxon at 0.1 µM induced a significant increase (more than 100%) in the twitch amplitude, while higher concentrations (0.3 and 1µM) induced partial or total contracture. Therefore, paraoxon at a concentration of 0.1 µ M was used to examine the capability of oximes to prevent or reverse its effects. Pralidoxime, obidoxime, and HI-6 dose-dependently prevented (when it was used as pre-treatment, 20 min before or at the same time of administration of the toxin) and reversed (when it was used as post-treatment, 20 min after the administration of the toxin) the effect of paraoxon. Conclusion: In conclusion, these results revealed that oximes were very useful in the prevention and reversal of the OP toxic effects on the skeletal muscle. Moreover, it was suggested that oximes were more effective when used as pre-treatment. Pralidoxime was more potent than obidoxime and HI-6. The HI-6, which is a newer oxime, was unexpectedly less effective than the other two.

scholarly journals Muscle-derived SDF-1α/CXCL12 modulates endothelial cell proliferation but not exercise training-induced angiogenesis

2019 ◽  
Vol 317 (6) ◽  
pp. R770-R779
Author(s):  
Mami Yamada ◽  
Chihiro Hokazono ◽  
Ken Tokizawa ◽  
Shuri Marui ◽  
Masahiro Iwata ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Proliferation ◽  
Endothelial Cell ◽  
Exercise Training ◽  
Contractile Activity ◽  
Capillary Density ◽  
Tube Formation ◽  
Endothelial Cell Migration ◽  
Endothelial Cell Proliferation ◽  
C2c12 Myotubes

Chemokines are critical mediators of angiogenesis in several physiological and pathological conditions; however, a potential role for muscle-derived chemokines in exercise-stimulated angiogenesis in skeletal muscle remains poorly understood. Here, we postulated that the chemokine stromal cell-derived factor-1 (SDF-1α/C-X-C motif chemokine ligand 12: CXCL12), shown to promote neovascularization in several organs, contributes to angiogenesis in skeletal muscle. We found that CXCL12 is abundantly expressed in capillary-rich oxidative soleus and exercise-trained plantaris muscles. CXCL12 mRNA and protein were also abundantly expressed in muscle-specific peroxisome proliferator-activated receptor γ coactivator 1α transgenic mice, which have a high proportion of oxidative muscle fibers and capillaries when compared with wild-type littermates. We then generated CXCL12 muscle-specific knockout mice but observed normal baseline capillary density and normal angiogenesis in these mice when they were exercise trained. To get further insight into a potential CXCL12 role in a myofiber-endothelial cell crosstalk, we first mechanically stretched C2C12 myotubes, a model known to induce stretch-related chemokine release, and observed increased CXCL12 mRNA and protein. Human umbilical vein endothelial cells (HUVECs) exposed to conditioned medium from cyclically stretched C2C12 myotubes displayed increased proliferation, which was dependent on CXCL12-mediated signaling through the CXCR4 receptor. However, HUVEC migration and tube formation were unaltered under these conditions. Collectively, our findings indicate that increased muscle contractile activity enhances CXCL12 production and release from muscle, potentially contributing to endothelial cell proliferation. However, redundant signals from other angiogenic factors are likely sufficient to sustain normal endothelial cell migration and tube formation activity, thereby preserving baseline capillary density and exercise training-mediated angiogenesis in muscles lacking CXCL12.

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