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Local kallikrein-kinin system is involved in podocyte apoptosis under diabetic conditions

 Seung-Jae Kwak  ;  Jisun Paeng  ;  Do Hee Kim  ;  Sun Ha Lee  ;  Bo-Young Nam  ;  Hye Young Kang  ;  Jin Ji Li  ;  Dong-Sub Jung  ;  Seung Hyeok Han  ;  Dong-Ryeol Ryu  ;  Jung Tak Park  ;  Tae Ik Chang  ;  Tae-Hyun Yoo  ;  Dae Suk Han  ;  Shin-Wook Kang 
 APOPTOSIS, Vol.16(5) : 478-490, 2011 
Journal Title
Issue Date
Animals ; Apoptosis*/drug effects ; Bradykinin/pharmacology ; Bradykinin/physiology* ; Cytoprotection ; Diabetes Mellitus, Experimental/chemically induced ; Diabetes Mellitus, Experimental/metabolism* ; Diabetes Mellitus, Experimental/pathology ; Diabetic Nephropathies/metabolism* ; Diabetic Nephropathies/pathology ; Gene Expression ; Glucose/metabolism ; Kallikrein-Kinin System* ; Male ; Mice ; Podocytes/drug effects ; Podocytes/metabolism* ; Podocytes/pathology ; Rats ; Rats, Sprague-Dawley
Diabetic nephropathy ; Kallikrein–kinin system ; p38 MAPK ; Podocyte ; Apoptosis
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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kang, Shin Wook(강신욱) ORCID logo https://orcid.org/0000-0002-5677-4756
Kang, Hye Young(강혜영)
Kwak, Seung Jae(곽승재)
Kim, Do Hee(김도희)
Nam, Bo Young(남보영)
Park, Jung Tak(박정탁) ORCID logo https://orcid.org/0000-0002-2325-8982
Yoo, Tae Hyun(유태현) ORCID logo https://orcid.org/0000-0002-9183-4507
Chang, Tae Ik(장태익)
Jung, Dong Sub(정동섭)
Paeng, Ji Sun(팽지선)
Han, Dae Suk(한대석)
Han, Seung Hyeok(한승혁) ORCID logo https://orcid.org/0000-0001-7923-5635
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