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1 and clusterin in the
hydronephrotic neonatal rat kidney
1 Department of Pediatrics, Korea University, Seoul, Korea 152-703; and 2 Department of Pediatrics, University of Virginia, Charlottesville, Virginia 22908
Unilateral ureteral obstruction (UUO)
induces activation of the renin-angiotensin system and upregulation of
transforming growth factor-
1 (TGF-1; 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-1 and clusterin by ANG II in the
neonatal rat. Animals were subjected to UUO in the first 2 days of
life, and renal TGF-1 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-1
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.
AT1 receptors; AT2 receptors; losartan; PD-123319
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