THE AGE-RELATED INCREASE IN RENAL CLUSTERIN MESSENGER-RNA IS ACCELERATED IN OBESE ZUCKER RATS

Clusterin is a multifunctional glycoprotein associated with developmen t and tissue injury. Because renal function decreases with advancing a ge in the obese Zucker rat, clusterin mRNA expression was examined in the kidney of young adult Zucker rats and compared with age-related ch anges in renal clusterin mRNA expression in Fischer 344 (F344) rats. R enal clusterin mRNA levels in the obese Zucker rat were 2.5-fold highe r by 3 mo of age and fourfold higher at 5 mo of age compared with the lean strain. In comparison, renal clusterin mRNA in 12-mo-old F344 rat s was twofold higher than in 3-mo-old animals and was tenfold higher a t 24 mo of age. Clusterin mRNA was positively correlated with urinary protein excretion and negatively correlated with creatinine clearance in Zucker rats. Clusterin was increased in select nephrons of the obes e Zucker rat kidney and in 24-mo-old F344 rat kidney as assessed by in situ hybridization. Increased expression of clusterin mRNA occurred m ostly in the tubular epithelium of dilated, convoluted proximal tubule s. These data indicate that renal clusterin mRNA levels increase as a function of age and that age-related increases in renal clusterin and the associated tubular abnormalities are accelerated in obese Zucker r ats.