Angiotensin II regulates migration in mouse cultured mesangial cells: evidence for the presence of receptor subtype-specific regulation.
The biological effects of angiotensin II (AngII) are mediated by two major subtypes of AngII receptors, type 1 (AT1R) and type 2 (AT2R). In this study, we attempted to elucidate the role of AngII subtype receptor-specific regulation in migration and proliferation of mouse cultured mesangial (MSG) cells. We found that 100 nM AngII stimulated weak migration of MSG cells. Cell motility increased more in the presence of AT2R than in the presence of AT1R, and it was suppressed by guanylate cyclase inhibitors. On the other hand, the activation of AT1R resulted in increased cell numbers, while AT2R activation inhibited cell proliferation. Moreover, high concentrations of glucose (25 mM) stimulated the expression of AT2R but not AT1R. These results indicate that there are receptor subtype-specific roles in MSG cells, and it is therefore possible that the activation of AT2R stimulates repair of glomerular tissue defect, by regulation of migration and proliferation of MSG cells. Taken together, these results suggest that the relative concentrations of AT1R and AT2R are important factors in the regulation of AngII function in glomerular tissue, and alterations in the concentrations of these receptors may contribute to progression of or protection from diabetic nephropathy.
Takeuchi
Yuichiro
Y
Department of Aging Medicine and Geriatrics, Graduate School of Medicine, Shinshu University, 3-1-1, Asahi, Matsumoto-Shi, Nagano 390-8621, Japan. takeuti@hsp.md.shinshu-u.ac.jp
Yamauchi
Keishi
K
Nakamura
Junko
J
Shigematsu
Satoshi
S
Hashizume
Kiyoshi
K
D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001667:Binding, Competitive; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D007093:Imidazoles / Q000494:pharmacology; D015151:Immunoblotting; D050527:Mesangial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; C437965:olmesartan