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

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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 languageEnglish
Pages (from-to)478-490
Number of pages13
JournalApoptosis
Volume16
Issue number5
DOIs
Publication statusPublished - 2011 May 1

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

Cite this

Kwak, S. J., Paeng, J., Kim, D. H., Lee, S. H., Nam, B. Y., Kang, H. Y., Li, J. J., Jung, D. S., Han, S. H., Ryu, D. R., Park, J. T., Chang, T. I., Yoo, T. H., Han, D. S., & Kang, S. W. (2011). Local kallikrein-kinin system is involved in podocyte apoptosis under diabetic conditions. Apoptosis, 16(5), 478-490. https://doi.org/10.1007/s10495-011-0585-1