Angiotensin stimulates TGF-beta 1 and clusterin in the hydronephrotic neonatal rat kidney

Unilateral ureteral obstruction (UUO) induces activation of the renin-angio tensin system and upregulation of transforming growth factor-beta 1 (TGF-be ta 1; a cytokine modulating cellular adhesion and fibrogenesis) and cluster in (a glycoprotein produced in response to cellular injury). This study was designed to examine the regulation of renal TGF-beta 1 and clusterin by AN G II in the neonatal rat. Animals were subjected to UUO in the first 2 days of life, and renal TGF-beta 1 and clusterin mRNA were measured 3 days late r rats were divided into treatment groups receiving saline vehicle, ANG, lo sartan (AT(1) receptor inhibitor), or PD-123319 (AT(2) receptor inhibitor). ANG stimulated renal TGF-beta 1 expression via AT(1) receptors, a response similar to that in the adult. In contrast, clusterin expression was stimul ated via AT(2) receptors, a response differing from that in the adult, in w hich ANG inhibits clusterin expression via AT(1) receptors. We speculate th at the unique response of the neonatal hydronephrotic kidney to ANG II is d ue to the preponderance of AT(2) receptors in the developing kidney.