Angiotensin II type 1 and type 2 receptors play opposite roles in regulating the barrier function of kidney glomerular capillary wall.
Although angiotensin II (Ang II) type 1 receptor antagonist ameliorates proteinuria, its pharmacological mechanism and the differential roles of Ang II type 1 receptor (AT1R) and type 2 receptor (AT2R) are not well understood. We analyzed the effect of Ang II type 1 receptor antagonist on proteinuria caused by antibody against nephrin, a functional molecule of glomerular slit diaphragm and dysfunction of which is involved in the development of proteinuria in several glomerular diseases. We show here that AT1R antagonist ameliorated proteinuria by preventing a reduction in the functional molecules of the slit diaphragm. We also analyzed the role of AT1R- or AT2R-mediated actions on the expression of the slit diaphragm molecules in an in vivo study of normal rat and in an in vitro study of cultured podocytes. AT1R-mediated action hampered the mRNA expression of the slit diaphragm molecules, whereas AT2R-mediated action enhanced it. These findings indicate that Ang II receptor subtypes play opposite roles in regulating the barrier function of glomerular capillary wall and that the enhancement of AT2R stimulation may serve as a potential therapeutic strategy for proteinuria.
Suzuki
Koichi
K
Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata, 951-8510, Japan.
Han
Gi Dong
GD
Miyauchi
Naoko
N
Hashimoto
Taeko
T
Nakatsue
Takeshi
T
Fujioka
Yumiko
Y
Koike
Hiroko
H
Shimizu
Fujio
F
Kawachi
Hiroshi
H
D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000378:metabolism; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000633:toxicity; D002196:Capillaries / Q000166:cytology / Q000378:metabolism; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D050199:Podocytes / Q000166:cytology / Q000378:metabolism*; D011507:Proteinuria; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D000911:Antibodies, Monoclonal; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D010750:Phosphoproteins; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012795:Sialoglycoproteins; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; C113267:nephrin; C001643:podocalyxin; D000804:Angiotensin II