TY - JOUR
T1 - High glucose and angiotensin II increase β1 integrin and integrin-linked kinase synthesis in cultured mouse podocytes
AU - Han, Sang Youb
AU - Kang, Young Sun
AU - Jee, Yi Hwa
AU - Han, Kum Hyun
AU - Cha, Dae Ryong
AU - Kang, Shin Wook
AU - Han, Dae Suk
N1 - Funding Information:
The results presented in this paper have not been published previously in whole or part, except in abstract form. This work was supported by grant R01–2002–000–00139–0 from the Basic Research Program of the Korea Science & Engineering Foundation.
PY - 2006/2
Y1 - 2006/2
N2 - 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/1 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.
AB - 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/1 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.
KW - Diabetes mellitus
KW - Integrin beta 1
KW - Integrin-linked kinase
KW - Mouse (immortalized podocyte cell line)
KW - Podocyte
UR - http://www.scopus.com/inward/record.url?scp=30744434618&partnerID=8YFLogxK
U2 - 10.1007/s00441-005-0065-4
DO - 10.1007/s00441-005-0065-4
M3 - Article
C2 - 16189717
AN - SCOPUS:30744434618
VL - 323
SP - 321
EP - 332
JO - Cell and Tissue Research
JF - Cell and Tissue Research
SN - 0302-766X
IS - 2
ER -