Molecular Pathological Evaluation of Clusterin in a Rat Model of Unilateral Ureteral Obstruction as a Possible Biomarker of Nephrotoxicity

Abstract

In the present study, to determine the validity of considering clusterin as a possible biomarker of nephrotoxicity, the expression and distribution of clusterin in the rat UUO kidney were investigated. Real-time RT-PCR revealed an immediate increase in the clusterin mRNA level in the kidney, within 6 hours after UUO, and also maintenance of the mRNA expression level from day-1 to day-3 was 60-fold higher in the UUO kidney than in the sham kidney. ISH analysis revealed clusterin mRNA signals in the UUO renal tubular epithelium, whereas no signal was observed in the sham kidney. Detection of clusterin-alpha and -beta was conducted using the subtype-specific antibodies, by both of western blotting and immunohistochemistry. Although clusterin-alpha was predominant in the UUO urine, only faint signals were noted at the brush border of the tubular epithelium or intraductal. On the other hand, strong signals of clusterin-beta were detected in the UUO kidney homogenate, and the molecule was localized in the renal tubular epithelium. These results suggest that clusterin was translated in the renal tubular epithelium after de novo expression induced by renal injury. Thus, detection of clusterin mRNA and clusterin-beta in the kidney or clusterin-alpha in the urine may be useful for predicting nephrotoxicity.

Early Predictors of Acute Kidney Injury: A Narrative Review

“…In AKI caused by nephrectomy, polycystic kidney, and renal cell carcinoma, the expression of clusterin on dedifferentiated tubular cells was significantly increased as KIM-1 [112]. One study found that in a rat model of unilateral ureteral obstruction, the clusterin mRNA expression was significantly increased in injured renal tubular epithelial cells, and its content in urine elevated at the same time, suggesting that clusterin can serve as an early biomarker of AKI [113]. The renal tissue still maintains the normal morphology when clusterin emerges in tubular injury location, and thus it can be used as an early marker of renal damage.…”

Clusterin Attenuates the Development of Renal Fibrosis

“…[24][25][26][27][28] Clusterin is expressed particularly in the renal tubular epithelium after renal injury and UUO. 27 Clusterin has been shown to be protective against gentamicin-induced renal tubular cell injury 29 and to protect against oxidative stress. 30 Based on these data, we reasoned that, in experimental renal fibrosis models, the upregulation of clusterin would function as a defense mechanism to prevent renal fibrosis.…”

Use of urinary renal biomarkers to evaluate the nephrotoxic effects of melamine or cyanuric acid in non-pregnant and pregnant rats

“…Following renal injury and during tubule repair/regeneration, Kim-1, clusterin, and osteopontin expression and protein levels markedly increase and can be detected in urine (Bonventre, 2009;Ishii et al, 2007;Ozer et al, 2010). Each of these proteins has been associated with renal tubule injury and contributes to the restoration of the cellular architecture and function of tubule epithelium following toxic insults (Bonventre, 2003;Harpur et al, 2011;Ichimura et al, 2004;Rouse et al, 2011;Wang et al, 2008).…”