| [ Summary ] |
Erythropoietin (Epo) gene expression is positively regulated by hypoxia-inducible factor-1, which binds to the 3´ enhancer of the Epo gene. Epo gene expression is also negatively regulated by GATA, which binds to the GATA site in the 5´ promoter NG-monomethyl L-arginine (L-NMMA), which competes with L-arginine as a substrate for nitric oxide synthase (NOS), is undetectable in non-uremic subjects, but is markedly elevated in patients with chronic renal failure. L-NMMA suppresses Epo gene expression by up-regulating GATA through the suppression of NO・cGMP production and inhibits Epo promoter activity. This is because Epo gene expression is negatively regulated by the binding of GATA to the GATA site of Epo promoter. Oral administration of 1.3 g / day of L-arginine can significantly improve Epo production and reverse anemia without adverse effects in patients with renal disease anemia who are in a predialysis state of chronic renal failure. K-7174 (a GATA specific inhibitor) improves Epo production when Epo production is inhibited by L-NMMA in Hep3B cells. As a result, this raises the possibility of using K-7174 as a novel drug for improving renal disease anemia. |