Anti-inflammatory and renal protective actions of stanniocalcin-1 in a model of anti-glomerular basement membrane glomerulonephritis

Am J Pathol. 2009 Apr;174(4):1368-78. doi: 10.2353/ajpath.2009.080476. Epub 2009 Feb 26.

Abstract

We have previously shown that stanniocalcin-1 (STC1) inhibits the transendothelial migration of macrophages and T cells, suppresses superoxide generation in macrophages, and attenuates macrophage responses to chemoattractants. To study the effects of STC1 on inflammation, in this study we induced a macrophage- and T-cell-mediated model of anti-glomerular basement membrane disease in STC1 transgenic mice, which display elevated serum STC1 levels and preferentially express STC1 in both endothelial cells and macrophages. We examined the following parameters both at baseline and after anti-glomerular basement membrane antibody treatment: blood pressure; C(3a) levels; urine output; proteinuria; blood urea nitrogen; and kidney C(3) deposition, fibrosis, histological changes, cytokine expression, and number of T cells and macrophages. Compared with wild-type mice, after anti-glomerular basement membrane treatment STC1 transgenic mice exhibited: i) diminished infiltration of inflammatory macrophages in the glomeruli; ii) marked reduction in crescent formation and sclerotic glomeruli; iii) decreased interstitial fibrosis; iv) preservation of kidney function and lower blood pressure; v) diminished C(3) deposition in the glomeruli; and vi) reduced expression of macrophage inhibitory protein-2 and transforming growth factor-beta2 in the kidney. Compared with baseline, wild-type mice, but not STC1 transgenic mice, had higher proteinuria and a marked reduction in urine output. STC1 had minimal effects, however, on both T-cell number in the glomeruli and interstitium and on cytokine expression characteristic of either TH1 or TH2 activation. These data suggest that STC1 is a potent anti-inflammatory and renal protective protein.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Glomerular Basement Membrane Disease / immunology*
  • Anti-Glomerular Basement Membrane Disease / pathology
  • Autoantibodies / immunology
  • Autoantigens / immunology
  • Blotting, Western
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Disease Models, Animal
  • Glomerular Basement Membrane / immunology
  • Glomerular Basement Membrane / pathology
  • Glycoproteins / genetics
  • Glycoproteins / immunology*
  • Immunohistochemistry
  • Inflammation / immunology
  • Inflammation / pathology
  • Inflammation Mediators / immunology*
  • Kidney Function Tests
  • Mice
  • Mice, Transgenic

Substances

  • Autoantibodies
  • Autoantigens
  • Cytokines
  • Glycoproteins
  • Inflammation Mediators
  • antiglomerular basement membrane antibody
  • teleocalcin