Effects of hypoxia on growth factor expression in the rat kidney in vivo.
There is accumulating evidence from in vitro studies suggesting that the genes of endothelin-1, PDGF, and VEGF are, like the erythropoietin gene, regulated by oxygen tension and by divalent cations. Hypoxia-induced stimulation of, such as endothelin-1, PDGF or VEGF might be involved in the pathogenesis of acute or chronic renal failure, and in renal "inflammatory" diseases (glomerulonephritis, vasculitis, allograft rejection). Hypoxia (8% O2) for six hours caused a 55-fold/1.6-fold increase of renal erythropoietin/endothelin-1 gene expression, whereas endothelin-3, PDGF-A, PDGF-B, and VEGF gene expression was unchanged. Carbon monoxide (0.1%) treatment for six hours stimulated renal erythropoietin gene expression 140-fold; however, endothelin-1, endothelin-3, PDGF-A, PDGF-B, and VEGF gene expression was not affected. Finally, cobalt treatment (60 mg/kg CoCl2) increased only renal erythropoietin/PDGF-B gene expression 5-fold/1.65-fold. These findings suggest that hypoxia is a rather weak stimulus for renal endothelin-1 gene expression, and that renal PDGF and VEGF gene expression in vivo is not sensitive to tissue hypoxia, in contrast to cell culture experiments. The in vivo regulation of endothelin-1, PDGF, and VEGF differs substantially from that of erythropoietin, suggesting that the basic gene regulatory mechanisms may not be the same.
Krämer
B K
BK
Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Germany.
Bucher
M
M
Sandner
P
P
Ittner
K P
KP
Riegger
G A
GA
Ritthaler
T
T
Kurtz
A
A
D000818:Animals; D016228:Endothelial Growth Factors / Q000235:genetics; D019332:Endothelin-1 / Q000235:genetics; D019334:Endothelin-3 / Q000235:genetics; D004921:Erythropoietin / Q000235:genetics; D015870:Gene Expression; D006133:Growth Substances / Q000235:genetics*; D000860:Hypoxia / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000209:etiology; D008222:Lymphokines / Q000235:genetics; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D019332:Endothelin-1; D019334:Endothelin-3; D006133:Growth Substances; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C075278:platelet-derived growth factor A; D004921:Erythropoietin