| Original Article : Effect of Glomerular Cyclooxygenase-2 Overexpression on Podocyte Injury Induced by Puromycin in Mice |
| Young-Il Jo, M.D. |
| Division of Nephrology, Department of Internal Medicine, Konkuk University School of Medicine |
| 기초연구 : 생쥐에서 사구체내 Cyclooxygenase-2 과발현이 Puromycin에 의한 발세포 손상에 미치는 영향 |
| 조 영 일 |
| 건국대학교 의학전문대학원 신장내과 |
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| 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 (30mg/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.
Key Words : Cyclooxygenase-2, Podocyte, Nephrin, Puromycin. |
| Key Words:
Cyclooxygenase-2, Podocyte, Nephrin, Puromycin. |
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