High glucose and angiotensin II increase beta1 integrin and integrin-linked kinase synthesis in cultured mouse podocytes.
Alterations of integrin alpha3beta1 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 alpha3 and beta1, and whether these changes are associated with integrin-linked kinase (ILK) in cultured mouse podocytes. Integrin beta1 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 beta1 and ILK mRNA expression was significantly inhibited by treatment with losartan (100 muM). In addition, the up-regulation of ILK synthesis induced by these stimuli was related to beta1 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, beta1 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.
Han
Sang Youb
SY
Department of Internal Medicine, College of Medicine, Inje University, Seoul, South Korea.
Kang
Young Sun
YS
Jee
Yi Hwa
YH
Han
Kum Hyun
KH
Cha
Dae Ryong
DR
Kang
Shin Wook
SW
Han
Dae Suk
DS
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D015870:Gene Expression; D005947:Glucose / Q000494:pharmacology*; D019012:Integrin beta1 / Q000096:biosynthesis* / Q000235:genetics; D019808:Losartan / Q000494:pharmacology; D051379:Mice; D008856:Microscopy, Fluorescence; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D000099200:Scaffold Protein ILK
D000804:Angiotensin II; D047228:Angiotensin II Type 1 Receptor Blockers; D004338:Drug Combinations; D005947:Glucose; D019012:Integrin beta1; D019808:Losartan; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D000099200:Scaffold Protein ILK