Effect of Glomerular Cyclooxygenase-2 Overexpression on Podocyte Injury Induced by Puromycin in Mice.
- Author:
Young Il JO
1
Author Information
1. Division of Nephrology, Department of Internal Medicine, Konkuk University School of Medicine, Korea. nephjo@kuh.ac.kr
- Publication Type:Original Article
- Keywords:
Cyclooxygenase-2;
Podocyte;
Nephrin;
Puromycin
- MeSH:
Albuminuria;
Animals;
Cyclooxygenase 2*;
Foot;
Mice*;
Mice, Transgenic;
Podocytes*;
Puromycin Aminonucleoside;
Puromycin*;
Up-Regulation
- From:Korean Journal of Nephrology
2007;26(2):127-136
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: The aim of this study is to investigate the effect of glomerular cyclooxygenase-2 (COX-2) overexpression on podocyte injury by puromycin aminonucleoside (PAN) in nephrin-driven COX-2 transgenic mice. METHODS: We administrated PAN intravenously on day-1 (15 mg/100 g body weight) and day-3 (30 mg/100 g body weight) in wild type (male B6/D2 mice) and COX-2 transgenic mice. An additional group received a selective COX-2 inhibitor (SC58236) with PAN. The animals from each group were sacrificed at the end of day-3 and 10. We investigated albuminuria, foot process effacement and glomerular COX-2 and nephrin expression. RESULTS: PAN induced albuminuria only in COX-2 transgenic mice, with the peak on day-3. Selective COX-2 inhibition significantly reduced albuminuria. EM examination demonstrated foot process effacement, which was improved partially by selective COX-2 inhibition, in COX-2 transgenic mice treated with PAN on day-3. Glomerular COX-2 expression increased significantly on day-3 in COX-2 transgenic mice treated with PAN, whereas expression of nephrin showed a tendency to decrease on day-3. These changes of expression of COX-2 and nephrin were partly attenuated by selective COX- 2 inhibition. Unlike COX-2 transgenic mice, wild-type mice did not show any changes even after PAN treatment. CONCLUSION: In COX-2 transgenic mice, PAN induced albuminuria, podocyte injury and up-regulation of glomerular COX-2, which were ameliorated by selective COX-2 inhibitor. These results suggest that COX-2 may play an important role in increasing susceptibility of podocytes to injury and selective COX-2 inhibition may ameliorate podocyte injury.
