N-Acetyl-seryl-aspartyl-lysyl-proline Alleviates Renal Fibrosis Induced by Unilateral Ureteric Obstruction in BALB/C Mice

Mediators Inflamm. 2015:2015:283123. doi: 10.1155/2015/283123. Epub 2015 Oct 5.

Abstract

To expand the armamentarium of treatment for chronic kidney disease (CKD), we explored the utility of boosting endogenously synthesized N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), which is augmented by inhibition of the angiotensin converting enzyme. Male BALB/c mice underwent unilateral ureteral ligation (UUO) or sham operation and received exogenously administered Ac-SDKP delivered via a subcutaneous osmotic minipump or Captopril treatment by oral gavage. Seven days after UUO, there were significant reductions in the expression of both collagen 1 and collagen 3 in kidneys treated with Ac-SDKP or Captopril, and there was a trend towards reductions in collagen IV, α-SMA, and MCP-1 versus control. However, no significant attenuation of interstitial injury or macrophage infiltration was observed. These findings are in contrary to observations in other models and underscore the fact that a longer treatment time frame may be required to yield anti-inflammatory effects in BALB/c mice treated with Ac-SDKP compared to untreated mice. Finding an effective treatment regimen for CKD requires fine-tuning of pharmacologic protocols.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Animals
  • Captopril / chemistry
  • Chemokine CCL2 / metabolism
  • Collagen Type IV / metabolism
  • Fibrosis / drug therapy*
  • Immunohistochemistry
  • Inflammation
  • Kidney Diseases / drug therapy*
  • Lymphocytes / cytology
  • Macrophages / cytology
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Muscle, Smooth / metabolism
  • Oligopeptides / therapeutic use*
  • Real-Time Polymerase Chain Reaction
  • Ureteral Obstruction / drug therapy*

Substances

  • Actins
  • Angiotensin-Converting Enzyme Inhibitors
  • CCL2 protein, human
  • Chemokine CCL2
  • Collagen Type IV
  • Oligopeptides
  • Captopril
  • goralatide