Augmenter of liver regeneration protects kidneys from ischaemia/reperfusion injury in rats

Nephrol Dial Transplant. 2010 Sep;25(9):2921-9. doi: 10.1093/ndt/gfq151. Epub 2010 Mar 23.

Abstract

Background: Augmenter of liver regeneration (ALR), which was identified originally for its crucial role in promoting hepatocyte proliferation, is expressed in both the liver and kidney. Protective effects of ALR have been demonstrated in experimental models of acute liver failure. In the present study, we investigated the effect of ALR on renal ischaemia/reperfusion (I/R) injury and the possible mechanisms of its action.

Methods: Male Sprague-Dawley rats were subjected to renal ischaemia for 60 min and then administered with either saline or recombinant human ALR (rhALR). A sham-operated group served as control. The expression of ALR in the sham-operated and acute kidney injury (AKI) groups was detected by immunohistochemistry and western blotting. Renal dysfunction and injury were assessed by measurement of serum biochemical markers and histological grading. Expression of proliferating cell nuclear antigen (PCNA) was determined by immunohistochemistry.

Results: Renal ALR expression increased significantly in rats with ischaemic AKI compared with the sham-operated rats. Serum biochemical parameters showed that renal dysfunction was improved by administration of rhALR. Histological analysis revealed that treatment with rhALR also reduced the extent of kidney injury. Intraperitoneal injection of rhALR enhanced the proliferation of renal tubular cells. Conclusions. Administration of rhALR effectively reduces tubular injury and ameliorates the impairment of renal function. The protective effect of rhALR is associated with enhancement of renal tubular cell regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / metabolism*
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Blotting, Western
  • Cytochrome Reductases / genetics
  • Cytochrome Reductases / metabolism*
  • Hepatocytes / cytology
  • Hepatocytes / metabolism
  • Humans
  • Immunoenzyme Techniques
  • Kidney Function Tests
  • Male
  • Oxidoreductases Acting on Sulfur Group Donors
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Reperfusion Injury / complications
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / prevention & control*

Substances

  • Proliferating Cell Nuclear Antigen
  • Recombinant Proteins
  • Cytochrome Reductases
  • GFER protein, human
  • Oxidoreductases Acting on Sulfur Group Donors