Regulation of VEGF and bFGF mRNA expression and other proliferative compounds in skeletal muscle cells.
The role of muscle contraction, prostanoids, nitric oxide and adenosine in the regulation of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endothelial cell proliferative compounds in skeletal muscle cell cultures was examined. VEGF and bFGF mRNA, protein release as well as the proliferative effect of extracellular medium was determined in non-stimulated and electro-stimulated rat and human skeletal muscle cells. In rat skeletal muscle cells these aspects were also determined after treatment with inhibitors and/or donors of nitric oxide (NO), prostanoids and adenosine. Electro-stimulation caused an elevation in the VEGF and bFGF mRNA levels of rat muscle cells by 33% and 43% (P < 0.05), respectively, and in human muscle cells VEGF mRNA was elevated by 24%. Medium from electro-stimulated human, but not rat muscle cells induced a 126% higher (P < 0.05) endothelial cell proliferation than medium from non-stimulated cells. Cyclooxygenase inhibition of rat muscle cells induced a 172% increase (P < 0.05) in VEGF mRNA and a 104% increase in the basal VEGF release. Treatment with the NO donor SNAP (0.5 microM) decreased (P < 0.05) VEGF and bFGF mRNA by 42 and 38%, respectively. Medium from SNAP treated muscle cells induced a 45% lower (P < 0.05) proliferation of endothelial cells than control medium. Adenosine enhanced the basal VEGF release from muscle cells by 75% compared to control. The present data demonstrate that contractile activity, NO, adenosine and products of cyclooxygenase regulate the expression of VEGF and bFGF mRNA in skeletal muscle cells and that contractile activity and NO regulate endothelial cell proliferative compounds in muscle extracellular fluid.
Jensen
L
L
Copenhagen Muscle Research Centre, Institute of Exercise and Sport Science, University of Copenhagen, Copenhagen, Denmark.
Schjerling
P
P
Hellsten
Y
Y
D000241:Adenosine / Q000494:pharmacology / Q000502:physiology*; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D032342:Muscle Cells / Q000737:chemistry / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism; D011453:Prostaglandins / Q000494:pharmacology / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D011453:Prostaglandins; D012333:RNA, Messenger; C110881:S-nitro-N-acetylpenicillamine; D042461:Vascular Endothelial Growth Factor A; C523965:alpha,beta-methyleneadenosine 5'-diphosphate; D016222:Fibroblast Growth Factor 2; D019335:Nitroarginine; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; D011451:Prostaglandin-Endoperoxide Synthases; D010396:Penicillamine; D000241:Adenosine; D007213:Indomethacin