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

被引:55
作者
Han, SY
Kang, YS
Jee, YH
Han, KH
Cha, DR
Kang, SW
Han, DS
机构
[1] Univ Korea Hosp, Dept Internal Med, Ansan 425020, Kyungki Do, South Korea
[2] Inje Univ, Coll Med, Dept Internal Med, Seoul, South Korea
关键词
integrin beta 1; integrin-linked kinase; podocyte; diabetes mellitus; mouse (immortalized podocyte cell line);
D O I
10.1007/s00441-005-0065-4
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Alterations of integrin alpha 3 beta 1 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 alpha 3 and beta 1, and whether these changes are associated with integrin-linked kinase (ILK) in cultured mouse podocytes. Integrin beta 1 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 beta 1 and ILK mRNA expression was significantly inhibited by treatment with losartan (100 mu M). In addition, the up-regulation of ILK synthesis induced by these stimuli was related to beta 1 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, beta 1 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.
引用
收藏
页码:321 / 332
页数:12
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