TY - JOUR
T1 - Angiotensin stimulates TGF-β1 and clusterin in the hydronephrotic neonatal rat kidney
AU - Yoo, Kee Hwan
AU - Thornhill, Barbara A.
AU - Chevalier, Robert L.
PY - 2000/3
Y1 - 2000/3
N2 - Unilateral ureteral obstruction (UUO) induces activation of the renin- angiotensin system and upregulation of transforming growth factor-β1 (TGF- β1; a cytokine modulating cellular adhesion and fibrogenesis) and clusterin (a glycoprotein produced in response to cellular injury). This study was designed to examine the regulation of renal TGF-β1 and clusterin by ANG II in the neonatal rat. Animals were subjected to UUO in the first 2 days of life, and renal TGF-β1 and clusterin mRNA were measured 3 days later. Rats were divided into treatment groups receiving saline vehicle, ANG, losartan (AT1 receptor inhibitor), or PD-123319 (AT2 receptor inhibitor). ANG stimulated renal TGF-β1 expression via AT1 receptors, a response similar to that in the adult. In contrast, clusterin expression was stimulated via AT2 receptors, a response differing from that in the adult, in which ANG inhibits clusterin expression via AT1 receptors. We speculate that the unique response of the neonatal hydronephrotic kidney to ANG II is due to the preponderance of AT2 receptors in the developing kidney.
AB - Unilateral ureteral obstruction (UUO) induces activation of the renin- angiotensin system and upregulation of transforming growth factor-β1 (TGF- β1; a cytokine modulating cellular adhesion and fibrogenesis) and clusterin (a glycoprotein produced in response to cellular injury). This study was designed to examine the regulation of renal TGF-β1 and clusterin by ANG II in the neonatal rat. Animals were subjected to UUO in the first 2 days of life, and renal TGF-β1 and clusterin mRNA were measured 3 days later. Rats were divided into treatment groups receiving saline vehicle, ANG, losartan (AT1 receptor inhibitor), or PD-123319 (AT2 receptor inhibitor). ANG stimulated renal TGF-β1 expression via AT1 receptors, a response similar to that in the adult. In contrast, clusterin expression was stimulated via AT2 receptors, a response differing from that in the adult, in which ANG inhibits clusterin expression via AT1 receptors. We speculate that the unique response of the neonatal hydronephrotic kidney to ANG II is due to the preponderance of AT2 receptors in the developing kidney.
KW - AT receptors
KW - AT receptors
KW - Losartan
KW - PD-123319
UR - http://www.scopus.com/inward/record.url?scp=0343775774&partnerID=8YFLogxK
U2 - 10.1152/ajpregu.2000.278.3.r640
DO - 10.1152/ajpregu.2000.278.3.r640
M3 - Article
C2 - 10712283
AN - SCOPUS:0343775774
SN - 0363-6119
VL - 278
SP - R640-R645
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 3 47-3
ER -