Expression of Clusterin by Angiotensin II Infusion in the Kidney and the Heart of Rats

ABSTRACT

PURPOSE: Clusterin is a heterodimeric glycoprotein and its expression is related with tissue injury and apotosis. Angitensisn II(ANG II) is known to be associated with the progression of renal disease by inducing renal fibrosis and cell proliferation. This study was designed to investigate the relationship between ANG II and clusterin expression in the kindey and the heart. We also attempted to discriminate the effect of ANG II-mediated hypertension by experimenting with two doses of ANG II-one is high enough to cause hypertension, and the other is not. METHODS: Three groups of Sprague-Dawley rats received ANG II infusion by osmotic minipump at a dose of 50ng/min, 100ng/min and placebo infusion, respectively. After 7 days, their kidneys and hearts were harvested and underwent immunohistochemical staining, RT-PCR, and Western blotting of clusterin. RESULTS: There were no differences in body weight nor organ weight/body weight among the three groups. Blood pressures of control and low-dose ANG group were not changed throughout the study, but that of high-dose ANG group was increased significantly at day 3 and 7. Staining for renal clusterin was diffusely distributed over the cortex and medulla in all 3 groups, but the intensity of staining was different notably in the medulla of control group which showed stronger staining than the ANG II infused groups. Staining intensity was not significantly different between the low and high ANG groups in the heart and kidney. In the kidney, expression of clusterin mRNA and protein were decreased in low-and high-dose ANG groups compared with control. In the heart, expression of clusterin mRNA was decreased in the low- and high-dose ANG groups compared with control. CONCLUSION: We conclude that ANG II decreases clusterin expression in the kidney and heart regardless of systemic hypertension induced by ANG II.