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Angiotensin II receptor blocker inhibits p27Kip1 expression in glucose-stimulated podocytes and in diabetic glomeruli.

Authors
 ZHONG-GAO XU  ;  TAE-HYUN YOO  ;  DONG-RYEOL RYU  ;  HYEONG CHEON PARK  ;  SUNG KYU HA  ;  DAE SUK HAN  ;  SHARON G. ADLER  ;  RAMA NATARAJAN  ;  SHIN-WOOK KANG 
Citation
 KIDNEY INTERNATIONAL, Vol.67(3) : 944-952, 2005 
Journal Title
 KIDNEY INTERNATIONAL 
ISSN
 0085-2538 
Issue Date
2005
MeSH
Angiotensin II/analysis ; Angiotensin Receptor Antagonists* ; Animals ; Cell Cycle Proteins/antagonists & inhibitors* ; Cell Cycle Proteins/genetics ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p27 ; Diabetes Mellitus, Experimental/metabolism* ; Diabetic Nephropathies/prevention & control* ; Epithelial Cells/metabolism ; Glucose/pharmacology* ; Imidazoles/pharmacology* ; Kidney/pathology ; Kidney Glomerulus/cytology ; Kidney Glomerulus/metabolism* ; Male ; Mice ; Rats ; Streptozocin ; Tetrazoles/pharmacology* ; Tumor Suppressor Proteins/antagonists & inhibitors* ; Tumor Suppressor Proteins/genetics
Keywords
p27Kip1 ; angiotensin II receptor blocker ; high glucose ; diabetic nephropathy ; podocytes ; hypertrophy
Abstract
BACKGROUND: Diabetic nephropathy is characterized by glomerular and tubular hypertrophy, and angiotensin II receptor blockers (ARBs) are known to prevent renal hypertrophy in diabetic patients. METHODS: To determine the effect of ARB on podocyte p27(Kip1) mRNA and protein expression, podocytes were exposed to 5.6 mmol/L normal glucose or 25 mmol/L high glucose with or without ARB, 10(-7) mol/L L-158,809. For animal studies, streptozotocin-induced diabetic rats were left untreated or were treated with 1 mg/kg/day L-158,809 for 3 months (diabetes mellitus + ARB). Competitive reverse transcription-polymerase chain reaction (RT-PCR), Western blot, immunohistochemistry, and morphometric analyses were performed. RESULTS: p27(Kip1) mRNA and protein expression in podocytes exposed to high glucose and in 3-month diabetic glomeruli were significantly increased (P < 0.01). High glucose significantly increased angiotensin II levels both in cell lysates and in media compared with normal glucose (P < 0.05) and exogenous angiotensin II also increased p27(Kip1) mRNA and protein expression in podocytes. L-158,809 treatment in podocytes inhibited the increase in p27(Kip1) mRNA expression by 84%, and protein expression by 89% (P < 0.05). p27(Kip1) mRNA and protein expression in diabetic + ARB glomeruli were also significantly reduced by 78% and 85%, respectively, compared with diabetic glomeruli (P < 0.01). ARB treatment also significantly ameliorated increased glomerular p27(Kip1) expression in diabetes mellitus as assessed by immunohistochemistry (P < 0.01). The increase in glomerular volume in diabetes mellitus was also inhibited by 81% with ARB treatment (P < 0.05). CONCLUSION: p27(Kip1) mRNA and protein expression were increased in diabetic glomeruli as well as in high glucose-stimulated podocytes, and this increment in p27(Kip1) expression was ameliorated by ARB treatment. These findings indicate that ARB treatment has an additional effect on preventing renal hypertrophy in diabetes mellitus.
Full Text
http://www.nature.com/ki/journal/v67/n3/full/4495127a.html
DOI
10.1111/j.1523-1755.2005.00158.x
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Shin Wook(강신욱) ORCID logo https://orcid.org/0000-0002-5677-4756
Ryu, Dong Ryeol(류동열)
Park, Hyeong Cheon(박형천) ORCID logo https://orcid.org/0000-0002-1550-0812
Yoo, Tae Hyun(유태현) ORCID logo https://orcid.org/0000-0002-9183-4507
Ha, Sung Kyu(하성규)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/151180
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