VEGF gene expression is upregulated in electrically stimulated rat skeletal muscle

1995 ◽  
Vol 269 (5) ◽  
pp. H1827-H1831 ◽  
Author(s):  
J. Hang ◽  
L. Kong ◽  
J. W. Gu ◽  
T. H. Adair
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Motor Nerve ◽  
Physiological Role ◽  
Northern Analysis ◽  
Mrna Levels ◽  
Vascular Endothelial ◽  
Vegf Gene ◽  
Vegf Expression ◽  
Vegf Mrna

Vascular endothelial growth factor (VEGF; also called vascular permeability factor) is a secreted mitogen with distinct target cell specificity for vascular endothelial cells. Hypoxia upregulates VEGF expression, making it a likely mediator of the angiogenesis that occurs in poorly perfused tissues. The purpose of this study was to determine whether VEGF gene expression is upregulated in chronically stimulated skeletal muscles, where hypoxia is thought to trigger the growth of blood vessels. The right anterior tibialis and extensor digitorum longus muscles of 12 rats were stimulated electrically (10 Hz, 300 microseconds pulses) for up to 21 days by way of the peroneal motor nerve. The contralateral muscles served as control. Northern analysis showed that VEGF mRNA levels increased by approximately sixfold after 4 days of stimulation and then decreased gradually over the next several days. VEGF mRNA levels were still elevated by two- to threefold after 21 days of stimulation. Higher VEGF mRNA levels in the early stages of muscle stimulation and gradually decreasing levels in later stages are consistent with a metabolic hypothesis in which tissue oxygenation controls VEGF expression. These studies support the hypothesis that VEGF has a physiological role in promoting angiogenesis in stimulated skeletal muscle.

scholarly journals Regulation of VEGF Gene Expression in Mouse Macrophages by Cottonseed Extracts, Gossypol and Lipopolysaccharides (P06-035-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Heping Cao ◽  
Kandan Sethumadhavan
Keyword(s):  
Gene Expression ◽  
Equal Opportunity ◽  
Angiogenic Factor ◽  
Mrna Levels ◽  
Vegf Gene ◽  
Vegf Mrna ◽  
Funding Sources ◽  
Raw264.7 Macrophages ◽  
Mouse Macrophages ◽  
Vegf Protein

Abstract Objectives Vascular endothelial growth factor (VEGF) is a key mediator of adipogenesis and a mitogenic and angiogenic factor involved in inflammation, tumor progression, collateral vessel formation, and diabetic retinopathy. VEGFa and VEGFb play a balance role in adipose differentiation and gene expression. Plant extracts and chemical compounds that can regulate VEGF gene expression may have positive effect on nutrition and health. The objective was to investigate the regulation of VEGF gene expression by cottonseed extracts, gossypol and lipopolysaccharides (LPS) in mouse RAW264.7 macrophages. Methods Mouse RAW264.7 macrophages were treated with various concentrations of cottonseed extracts, gossypol and LPS for 2, 8 and 24 h. qPCR and immunoblotting were used to detect the expression of VEGF mRNA and protein. Results qPCR assay showed that cottonseed extracts exhibited modest effects on VEGF gene expression with significant increases in VEGFa mRNA by glanded coat extract and VEGFb mRNA by glanded kernel and glandless coat extracts. Immunoblotting showed that only glandless seed extracts modestly increased VEGF protein. Gossypol stimulated VEGFa and VEGFb mRNA levels by 30- and 4-fold, respectively, and increased VEGF protein in macrophages. LPS increased VEGFa mRNA by 6-fold but decreased VEGFb mRNA under higher concentration for longer treatment. LPS increased VEGF protein in 2–4 h but decreased in 8–24 h. Conclusions These results demonstrate that cottonseed extracts have modest effect but gossypol and LPS have strong effect on VEGF gene expression in mouse macrophages. Funding Sources This work was supported by the USDA-ARS Quality and Utilization of Agricultural Products National Program 306 through CRIS 6054–41,000-103–00-D. USDA is an equal opportunity provider and employer.

Human VEGF gene expression in skeletal muscle: effect of acute normoxic and hypoxic exercise

1999 ◽  
Vol 277 (6) ◽  
pp. H2247-H2252 ◽  
Author(s):  
R. S. Richardson ◽  
H. Wagner ◽  
S. R. D. Mudaliar ◽  
R. Henry ◽  
E. A. Noyszewski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Acute Exercise ◽  
Work Rate ◽  
Northern Analysis ◽  
Endothelial Cell Proliferation ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels ◽  
Vegf Mrna ◽  
Exercise Induced

Vascular endothelial growth factor (VEGF) is involved in extracellular matrix changes and endothelial cell proliferation, both of which are precursors to new capillary growth. Angiogenesis is a vital adaptation to exercise training, and the exercise-induced reduction in intracellular[Formula: see text] has been proposed as a stimulus for this process. Thus we studied muscle cell[Formula: see text] [myoglobin[Formula: see text]([Formula: see text])] during exercise in normoxia and in hypoxia (12% O2) and studied the mRNA levels of VEGF in six untrained subjects after a single bout of exercise by quantitative Northern analysis. Single-leg knee extension provided the acute exercise stimulus: a maximal test followed by 30 min at 50% of the peak work rate achieved in this graded test. Because peak work rate was not affected by hypoxia, the absolute and relative work rates were identical in hypoxia and normoxia. Three pericutaneous needle biopsies were collected from the vastus lateralis muscle, one at rest and then the others at 1 h after exercise in normoxia or hypoxia. At rest (control), VEGF mRNA levels were very low (0.38 ± 0.04 VEGF/18S). After exercise in normoxia or hypoxia, VEGF mRNA levels were much greater (16.9 ± 6.7 or 7.1 ± 1.8 VEGF/18S, respectively). In contrast, there was no measurable basic fibroblast growth factor mRNA response to exercise at this 1-h postexercise time point. Magnetic resonance spectroscopy of myoglobin confirmed a reduction in[Formula: see text] in hypoxia (3.8 ± 0.3 mmHg) compared with normoxia (7.2 ± 0.6 mmHg) but failed to reveal a relationship between [Formula: see text] during exercise and VEGF expression. This VEGF mRNA increase in response to acute exercise supports the concept that VEGF is involved in exercise-induced skeletal muscle angiogenesis but questions the importance of a reduced cellular [Formula: see text]as a stimulus for this response.

scholarly journals Hypoxic Regulation of Vascular Endothelial Growth Factor mRNA Stability Requires the Cooperation of Multiple RNA Elements

1999 ◽  
Vol 10 (4) ◽  
pp. 907-919 ◽  
Author(s):  
J. A. Dibbens ◽  
D. L. Miller ◽  
A. Damert ◽  
W. Risau ◽  
M. A. Vadas ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Coding Region ◽  
Vegf Gene ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Rapid Degradation ◽  
Multiple Regions ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is a key regulator of developmental, physiological, and tumor angiogenesis. Upregulation of VEGF expression by hypoxia appears to be a critical step in the neovascularization of solid cancers. The VEGF mRNA is intrinsically labile, but in response to hypoxia the mRNA is stabilized. We have systematically analyzed the regions in the VEGF mRNA that are responsible for its lability under normoxic conditions and for stabilization in response to hypoxia. We find that the VEGF mRNA not only contains destabilizing elements in its 3′ untranslated region (3′UTR), but also contains destabilizing elements in the 5′UTR and coding region. Each region can independently promote mRNA degradation, and together they act additively to effect rapid degradation under normoxic conditions. Stabilization of the mRNA in response to hypoxia is completely dependent on the cooperation of elements in each of the 5′UTR, coding region, and 3′UTR. Combinations of any of two of these three regions were completely ineffective in responding to hypoxia, whereas combining all three regions allowed recapitulation of the hypoxic stabilization seen with the endogenous VEGF mRNA. We conclude that multiple regions in the VEGF mRNA cooperate both to ensure the rapid degradation of the mRNA under normoxic conditions and to allow stabilization of the mRNA in response to hypoxia. Our findings highlight the complexity of VEGF gene expression and also reveal a mechanism of gene regulation that could become the target for strategies of therapeutic intervention.

BCR/ABL induces expression of vascular endothelial growth factor and its transcriptional activator, hypoxia inducible factor-1α, through a pathway involving phosphoinositide 3-kinase and the mammalian target of rapamycin

Blood ◽  
2002 ◽  
Vol 100 (10) ◽  
pp. 3767-3775 ◽  
Author(s):  
Matthias Mayerhofer ◽  
Peter Valent ◽  
Wolfgang R. Sperr ◽  
James D. Griffin ◽  
Christian Sillaber
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Mammalian Target Of Rapamycin ◽  
Hypoxia Inducible Factor ◽  
Vascular Endothelial ◽  
Vegf Gene ◽  
Vegf Mrna ◽  
Phosphoinositide 3 Kinase ◽  
Endothelial Growth Factor

Recent data suggest that vascular endothelial growth factor (VEGF), a cytokine involved in autocrine growth of tumor cells and tumor angiogenesis, is up-regulated and plays a potential role in myelogenous leukemias. In chronic myelogenous leukemia (CML), VEGF is expressed at high levels in the bone marrow and peripheral blood. We show here that the CML-associated oncogene BCR/ABL induces VEGF gene expression in growth factor–dependent Ba/F3 cells. Whereas starved cells were found to contain only baseline levels of VEGF mRNA, Ba/F3 cells induced to express BCR/ABL exhibited substantial amounts of VEGF mRNA. BCR/ABL also induced VEGF promoter activity and increased VEGF protein levels in Ba/F3 cells. Moreover, BCR/ABL was found to promote the expression of functionally active hypoxia-inducible factor-1 (HIF-1), a major transcriptional regulator of VEGF gene expression. BCR/ABL-induced VEGF gene expression was counteracted by the phosphoinositide 3-kinase (PI3-kinase) inhibitor LY294002 and rapamycin, an antagonist of mammalian target of rapamycin (mTOR), but not by inhibition of the mitogen-activated protein kinase pathway. Similarly, BCR/ABL-dependent HIF-1α expression was inhibited by the addition of LY294002 and rapamycin. Together, our data show that BCR/ABL induces VEGF- and HIF-1α gene expression through a pathway involving PI3-kinase and mTOR. BCR/ABL-induced VEGF expression may contribute to the pathogenesis and increased angiogenesis in CML.

scholarly journals Enhanced Vascular Endothelial Growth Factor Gene Expression in Ischaemic Skin of Critical Limb Ischaemia Patients

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Silvia Bleda ◽  
Joaquín de Haro ◽  
Francisco Acin ◽  
César Varela ◽  
Leticia Esparza
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Critical Limb Ischaemia ◽  
Control Group ◽  
Venous Disease ◽  
Vascular Endothelial ◽  
Vegf Gene ◽  
Vegf Expression ◽  
Endothelial Growth Factor

Objectives. To perform a quantitative analysis of the vascular endothelial growth factor (VEGF) gene transcription in the skin of ischemic legs and provide information for VEGF in the pathogenesis in critical limb ischemia (CLI).Methods. Skin biopsies were obtained from 40 patients with CLI. Control samples came from 44 patients with chronic venous disease. VEGF gene expression was analysed using quantitative polymerase chain reaction.Results. Patients with CLI had higher skin VEGF expression than control group (RQ: 1.3 ± 0.1 versus 1,P=0.04).Conclusions. We found an association between ischemic skin and an elevated VEGF expression in legs from patients with CLI. These data support that the mechanism for VEGF upregulation in hypoxia conditions is intact and acts appropriately in the ischaemic limbs from patients with CLI.

scholarly journals The Effect of HRE-Regulated VEGF Expression and Transfection on Neural Stem Cells in Rats

2020 ◽  
Vol 8 ◽  
Author(s):  
Bo Dou ◽  
Xiangrong Zheng ◽  
Danfeng Tan ◽  
Xixi Yin
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Target Cells ◽  
Vascular Endothelial ◽  
Rt Pcr ◽  
Vegf Gene ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Endothelial Growth Factor ◽  
Vegf Protein

In this study, we analyzed neural stem cells transfected with the HRE-VEGF gene in groups experiencing different periods of hypoxia. The results of RT-PCR showed that the expression of vascular endothelial growth factor (VEGF) mRNA gradually increased with the prolonged period of hypoxia (p < 0.05). The results from the western-blot test showed that expression of the VEGF protein increased with as the period of hypoxia increased (p < 0.05). The results of MTT combined with Elisa reagent showed that with the prolonged period of hypoxia, the secretion of VEGF protein increased, and that the proliferation of target cells and neural stem cells was better promoted (p < 0.05). These results imply that HRE can safely and effectively regulate VEGF expression. By controlling the period of hypoxia, we can increase the expression level, and limit it in more safe values to avoid the possibility of cancer caused by the over-enhancement of proliferation of target cells due to the overexpression of the VEGF protein.

scholarly journals Retinoic Acid Pathway Regulation of Vascular Endothelial Growth Factor in Ovine Amnion

2018 ◽  
Vol 26 (10) ◽  
pp. 1351-1359 ◽  
Author(s):  
Cecilia Y. Cheung ◽  
Debra F. Anderson ◽  
Marion Rouzaire ◽  
Loïc Blanchon ◽  
Vincent Sapin ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Retinoic Acid ◽  
Growth Factor ◽  
Mrna Levels ◽  
Vascular Endothelial ◽  
Gene Promoters ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Pregnant Sheep ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) has been proposed as an important regulator of amniotic fluid absorption across the amnion into the fetal vasculature on the surface of the placenta. However, the activators of VEGF expression and action in the amnion have not been identified. Using the pregnant sheep model, we aimed to investigate the presence of the retinoic acid (RA) pathway in ovine amnion and to determine its effect on VEGF expression. Further, we explored relationships between RA receptors and VEGF and tested the hypothesis that RA modulates intramembranous absorption (IMA) through induction of amnion VEGF in sheep fetuses subjected to altered IMA rates. Our study showed that RA receptor isoforms were expressed in sheep amnion, and RA response elements (RAREs) were identified in ovine RARβ and VEGF gene promoters. In ovine amnion cells, RA treatment upregulated RARβ messenger RNA (mRNA) and increased VEGF transcript levels. In sheep fetuses, increases in IMA rate was associated with elevated VEGF mRNA levels in the amnion but not in the chorion. Further, RARβ mRNA was positively correlated with VEGF mRNA levels in the amnion and not chorion. We conclude that an RA pathway is present in ovine fetal membranes and that RA is capable of inducing VEGF. The finding of a positive relationship between amnion VEGF and RARβ during altered IMA rate suggests that the retinoid pathway may play a role through VEGF in regulating intramembranous transport across the amnion.

Skeletal muscle capillarity and angiogenic mRNA levels after exercise training in normoxia and chronic hypoxia

2001 ◽  
Vol 91 (3) ◽  
pp. 1176-1184 ◽  
Author(s):  
I. Mark Olfert ◽  
Ellen C. Breen ◽  
Odile Mathieu-Costello ◽  
Peter D. Wagner
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Factor ◽  
Exercise Training ◽  
Absolute Intensity ◽  
Mrna Levels ◽  
Rat Skeletal Muscle ◽  
Vegf Mrna ◽  
Hypoxic Training ◽  
Response To Exercise

Gene expression of vascular endothelial growth factor (VEGF), and to a lesser extent of transforming growth factor-β1 (TGF-β1) and basic fibroblast growth factor (bFGF), has been found to increase in rat skeletal muscle after a single exercise bout. In addition, acute hypoxia augments the VEGF mRNA response to exercise, which suggests that, if VEGF is important in muscle angiogenesis, hypoxic training might produce greater capillary growth than normoxic training. Therefore, we examined the effects of exercise training (treadmill running at the same absolute intensity) in normoxia and hypoxia (inspired O2 fraction = 0.12) on rat skeletal muscle capillarity and on resting and postexercise gene expression of VEGF, its major receptors (flt-1 and flk-1), TGF-β1, and bFGF. Normoxic training did not alter basal or exercise-induced VEGF mRNA levels but produced a modest twofold increase in bFGF mRNA ( P < 0.05). Rats trained in hypoxia exhibited an attenuated VEGF mRNA response to exercise (1.8-fold compared 3.4-fold with normoxic training; P< 0.05), absent TGF-β1 and flt-1 mRNA responses to exercise, and an approximately threefold ( P < 0.05) decrease in bFGF mRNA levels. flk-1 mRNA levels were not significantly altered by either normoxic or hypoxic training. An increase in skeletal muscle capillarity was observed only in hypoxically trained rats. These data show that, whereas training in hypoxia potentiates the adaptive angiogenic response of skeletal muscle to a given absolute intensity of exercise, this was not evident in the gene expression of VEGF or its receptors when assessed at the end of training.

scholarly journals Endocrine gland-derived vascular endothelial growth factor in rat pancreas: genetic expression and testosterone regulation

2008 ◽  
Vol 197 (2) ◽  
pp. 309-314 ◽  
Author(s):  
Angélica Morales ◽  
Sumiko Morimoto ◽  
Lorenza Díaz ◽  
Guillermo Robles ◽  
Vicente Díaz-Sánchez
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Pancreatic Tissue ◽  
Endocrine Gland ◽  
Vascular Endothelial ◽  
Rinm5f Cells ◽  
Vegf Gene ◽  
Rat Pancreas ◽  
Endothelial Growth Factor

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an endothelial cell mitogen, expressed essentially in steroidogenic cells. Recently, the expression of EG-VEGF in normal human pancreas and pancreatic adenocarcinoma has been demonstrated. Epidemiologically, pancreatic carcinogenesis is more frequent in males than females, and given that androgen receptors and testosterone biotransformation have been described in pancreas, we hypothesized that testosterone could participate in the regulation of EG-VEGF expression. In this study, we investigated the regulation of EG-VEGF gene expression by testosterone in normal rat pancreatic tissue and rat insulinoma cells (RINm5F). Total RNA was extracted from rat pancreas and cultured cells. Gene expression was studied by real-time PCR and protein detection by immunohistochemistry. Serum testosterone was quantified by RIA. Results showed that EG-VEGF is expressed predominantly in pancreatic islets and vascular endothelium, as well as in RINm5F cells. EG-VEGF gene expression was lower in the pancreas of rats with higher testosterone serum levels. A similar effect that was reverted by flutamide was observed in testosterone-treated RINm5F cells. In summary, testosterone down-regulated EG-VEGF gene expression in rat pancreatic tissue and RINm5F cells. This effect could be mediated by the androgen receptor. To our knowledge, this is the first time that a direct effect of testosterone on EG-VEGF gene expression in rat pancreas and RINm5F cells is demonstrated.

scholarly journals Myocyte vascular endothelial growth factor is required for exercise-induced skeletal muscle angiogenesis

2010 ◽  
Vol 299 (4) ◽  
pp. R1059-R1067 ◽  
Author(s):  
I. Mark Olfert ◽  
Richard A. Howlett ◽  
Peter D. Wagner ◽  
Ellen C. Breen
Keyword(s):  
Skeletal Muscle ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Exercise Training ◽  
Metabolic Adaptation ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Running Speed ◽  
Endothelial Growth Factor ◽  
Adaptation To Exercise

We have previously shown, using a Cre-LoxP strategy, that vascular endothelial growth factor (VEGF) is required for the development and maintenance of skeletal muscle capillarity in sedentary adult mice. To determine whether VEGF expression is required for skeletal muscle capillary adaptation to exercise training, gastrocnemius muscle capillarity was measured in myocyte-specific VEGF gene-deleted (mVEGF−/−) and wild-type (WT) littermate mice following 6 wk of treadmill running (1 h/day, 5 days/wk) at the same running speed. The effect of training on metabolic enzyme activity levels and whole body running performance was also evaluated in mVEGF−/− and WT mice. Posttraining capillary density was significantly increased by 59% ( P < 0.05) in the deep muscle region of the gastrocnemius in WT mice but did not change in mVEGF−/− mice. Maximal running speed and time to exhaustion during submaximal running increased by 20 and 13% ( P < 0.05), respectively, in WT mice after training but were unchanged in mVEGF−/− mice. Training led to increases in skeletal muscle citrate synthase (CS) and phosphofructokinase (PFK) activities in both WT and mVEGF−/− mice ( P < 0.05), whereas β-hydroxyacyl-CoA dehydrogenase (β-HAD) activity was increased only in WT mice. These data demonstrate that skeletal muscle capillary adaptation to physical training does not occur in the absence of myocyte-expressed VEGF. However, skeletal muscle metabolic adaptation to exercise training takes place independent of myocyte VEGF expression.

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