EFFECTS OF HYPOXIA ON GROWTH-FACTOR EXPRESSION IN THE RAT-KIDNEY IN-VIVO

Effects of hypoxia on renal growth factor expression in the rat kidney . There is accumulating evidence from in vitro studies suggesting that the genes of endothelin-1, PDGF, and VEGF are, like the erythropoieti n gene, regulated by oxygen tension and by divalent cations. Hypoxia-i nduced stimulation of, such as endothelin-1, PDGF or VEGF might be inv olved in the pathogenesis of acute or chronic renal failure, and in re nal ''inflammatory'' diseases (glomerulonephritis, vasculitis, allogra ft rejection). Hypoxia (8% O-2) for six hours caused a 55-fold/1.6-fol d increase of renal erythropoietin/endothelin-1 gene expression, where as endothelin-3, PDGF-A, PDGF-B, and VEGF gene expression was unchange d. Carbon monoxide (0.1%) treatment for six hours stimulated renal ery thropoietin gene expression 140-fold; however, endothelin-1, endotheli n-3, PDGF-A, PDGF-B, and VEGF gene expression was not affected. Finall y, cobalt treatment (60 mg/kg CoCl2) increased only renal erythropoiet in/PDGF-B gene expression 5-fold/1.65-fold. These findings suggest tha t hypoxia is a rather weak stimulus for renal endothelin-1 gene expres sion, and that renal PDGF and VEGF gene expression in vivo is not sens itive to tissue hypoxia, in contrast to cell culture experiments. The in vivo regulation of endothelin-1, PDGF, and VEGF differs substantial ly from that of erthropoietin, suggesting that the basic gene regulato ry mechanisms may not be the same.