Abstract
The kallikrein-kinin system (KKS) serves as the physiologic counterbalance to the renin-angiotensin system. This study was conducted to examine the changes in the expression of KKS components in podocytes under diabetic conditions and to elucidate the functional role of bradykinin (BK) in diabetes-associated podocyte apoptosis. Thirty-two rats were injected with either diluent (n = 16, C) or with streptozotocin intraperitoneally (n = 16, DM), and 8 rats from each group were treated with BK infusion for 6 weeks. Immortalized mouse podocytes were cultured in media containing 5.6 mmol/l glucose (NG), NG + 10-7 mol/l AII (AII), or 30 mmol/l glucose (HG) with or without 10-8 mol/l BK. Urinary albumin excretion was significantly higher in DM rats, and this increase was ameliorated by BK. Not only kininogen, kallikrein, and BK B1- and B2-receptor expression but also BK levels were significantly decreased in DM glomeruli and in cultured podocytes exposed to HG. The changes in the expressions of apoptosis-related molecules and the increase in the number of apoptotic cells in DM glomeruli as well as in HG- and AII-stimulated podocytes were significantly abrogated by BK. The suppressed KSS within podocytes under diabetic condition was associated with podocyte apoptosis, suggesting that BK may be beneficial in preventing podocyte loss in diabetic nephropathy.
Original language | English |
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Pages (from-to) | 478-490 |
Number of pages | 13 |
Journal | Apoptosis |
Volume | 16 |
Issue number | 5 |
DOIs | |
Publication status | Published - 2011 May |
Bibliographical note
Funding Information:Acknowledgments This work was supported in part by the BK21 (Brain Korea 21) Project for Medical Sciences, Yonsei University, and the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (R01-2007-000-20263-0 and R13-2002-054-04001-0).
All Science Journal Classification (ASJC) codes
- Pharmacology
- Pharmaceutical Science
- Clinical Biochemistry
- Cell Biology
- Biochemistry, medical
- Cancer Research