Temporal induction of clusterin in cisplatin nephrotoxicity

J Am Soc Nephrol. 1997 Feb;8(2):302-5. doi: 10.1681/ASN.V82302.

Abstract

Clusterin is a ubiquitous glycoprotein induced in many organs, including the kidney, at times of tissue injury and/or remodeling. It is speculated in this study that clusterin preserves cell interactions that are otherwise perturbed by renal insults. The purpose of this study was to examine clusterin expression after cisplatin nephrotoxicity, a model characterized by a delayed time course of injury and a well-defined site of that injury (proximal tubule). Sprague-Dawley rats were treated with intravenous cisplatin (6 mg/kg) or vehicle. Serum creatinine concentrations were measured and kidneys harvested at 1, 2, and 5 days. Marked induction of clusterin mRNA was seen only at 5 days, a time when serum creatinine concentration was the highest. Histology of kidney tissue 5 days after cisplatin administration revealed marked tubular necrosis localized to the outer stripe of the outer medulla, a region rich in proximal tubules. Immunohistochemistry and in situ hybridization at 5 days demonstrated clusterin primarily in the inner stripe of the outer medulla. In conclusion, expression of clusterin follows renal injury with cisplatin at a time corresponding to the morphologic evidence of tubular necrosis and cell detachment; quite surprisingly, such expression occurs at a site distant from the primary injury.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Cisplatin / toxicity*
  • Clusterin
  • Disease Models, Animal
  • Glycoproteins / biosynthesis*
  • Glycoproteins / genetics
  • Kidney / drug effects*
  • Kidney / injuries
  • Kidney / metabolism*
  • Molecular Chaperones*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Antineoplastic Agents
  • Clusterin
  • Glycoproteins
  • Molecular Chaperones
  • RNA, Messenger
  • Cisplatin