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High glucose and angiotensin II increase β1 integrin and integrin-linked kinase synthesis in cultured mouse podocytes

Authors
 Sang Youb Han  ;  Young Sun Kang  ;  Yi Hwa Jee  ;  Kum Hyun Han  ;  Dae Ryong Cha  ;  Shin Wook Kang  ;  Dae Suk Han 
Citation
 CELL AND TISSUE RESEARCH, Vol.323(2) : 321-332, 2006 
Journal Title
CELL AND TISSUE RESEARCH
ISSN
 0302-766X 
Issue Date
2006
MeSH
Angiotensin II/antagonists & inhibitors ; Angiotensin II/pharmacology* ; Angiotensin II Type 1 Receptor Blockers/pharmacology ; Animals ; Cell Adhesion/drug effects ; Cell Line, Transformed ; Dose-Response Relationship, Drug ; Drug Combinations ; Gene Expression ; Glucose/pharmacology* ; Integrin beta1/biosynthesis* ; Integrin beta1/genetics ; Losartan/pharmacology ; Mice ; Microscopy, Fluorescence ; Podocytes/metabolism* ; Podocytes/pathology ; Protein-Serine-Threonine Kinases/biosynthesis* ; Protein-Serine-Threonine Kinases/genetics ; RNA, Messenger/metabolism
Keywords
Integrin beta 1 ; Integrin-linked kinase ; Podocyte ; Diabetes mellitus ; Mouse (immortalized podocyte cell line)
Abstract
Alterations of integrin α3β1 may play a role in the development of diabetic nephropathy. We have investigated the effects of high glucose and angiotensin II on the expression of integrin α3 and β1, and whether these changes are associated with integrin-linked kinase (ILK) in cultured mouse podocytes. Integrin β1 and ILK mRNA expression and protein production were rapidly up-regulated in a dose-dependent manner by high glucose and angiotensin II stimulation. ILK mRNA levels in the mouse podocytes exposed to 30 mmol/l glucose were 1.66, 1.89, and 1.28 times higher than those in control cells at 6, 24, and 72 h exposure, respectively. ILK mRNA levels in mouse podocytes exposed to 1 nM, 10 nM, and 100 nM angiotensin II for 6 h were 1.38, 1.55, and 1.93 times higher, respectively, than those in control cells. Angiotensin-II-induced integrin β1 and ILK mRNA expression was significantly inhibited by treatment with losartan (100 μM). In addition, the up-regulation of ILK synthesis induced by these stimuli was related to β1 integrin synthesis and increased ILK kinase activity. Cell adhesion assay displayed inhibitory effects when podocytes were exposed to high concentrations of angiotensin II. Interestingly, glucose and angiotensin II stimulation induced shrinkage of the cell body and elongation of the podocyte processes, a phenotype similar to that of immature podocytes. In addition, β1 integrin showed higher levels of staining on both the cell membranes and the cell-cell contact areas. Thus, high glucose and angiotensin II may affect the regulation of the integrin-ILK system in podocytes; this system may therefore play a role in the pathogenesis of diabetic nephropathy and other renal diseases affecting podocytes.
Full Text
http://link.springer.com/article/10.1007%2Fs00441-005-0065-4
DOI
10.1007/s00441-005-0065-4
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
Han, Dae Suk(한대석)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/109019
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