Renal expression of angiotensin type 2 (AT2) receptors during kidney damage.
BACKGROUND
Activation of the renin angiotensin system has been described in pathologic conditions, including kidney damage. Angiotensin II (Ang II) acts through two receptors, AT1 and AT2. Most of the known actions of Ang II, including vasoconstriction and fibrosis, are due to AT1 activation. Recent data suggest that AT2 participates in the regulation of cell growth and renal inflammatory infiltration. Therefore, we investigated the renal expression of AT2 receptors in several models of renal injury.


METHODS
Investigations were done in the following experimental models of kidney damage: systemic infusion of Ang II (inflammation), folic acid nephropathy (tubular cell death), and protein overload proteinuria. AT2 expression was determined by immunohistochemistry (protein) and reverse transcription-polymerase chain reaction (RT-PCR) (gene).


RESULTS
In control animals, low levels of renal expression of AT2 were found. Ang II infusion resulted in an up-regulation of AT2 in tubular cells and de novo AT2 expression in glomeruli and vessels, associated with the presence of inflammatory cells. Acute tubular injury induced by folic acid was characterized by AT2 overexpression and apoptosis in tubular cells. Protein overload caused heavy proteinuria and tubular AT2 up-regulation.


CONCLUSIONS
AT2 is re-expressed in pathologic conditions of kidney damage, such as inflammation, apoptosis, and proteinuria, suggesting a potential role of this receptor during renal injury.
Ruiz-Ortega
Marta
M
Laboratory of Vascular and Renal Pathology, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain. mruizo@fid.es
Esteban
Vanesa
V
Suzuki
Yusuke
Y
Ruperez
Mónica
M
Mezzano
Sergio
S
Ardiles
Leopoldo
L
Justo
Pilar
P
Ortiz
Alberto
A
Egido
Jesús
J
D000804:Angiotensin II; D000818:Animals; D005492:Folic Acid; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D015854:Up-Regulation
D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D005492:Folic Acid