Expression of monocyte chemoattractant protein-1 in proximal tubular epithelial cells in a rat model of progressive kidney failure

J Lab Clin Med. 2002 Jul;140(1):43-51. doi: 10.1067/mlc.2002.125215.


Impairment of kidney function in various types of glomerular disease is associated with tubulointerstitial changes. Monocyte chemoattractant protein-1 (MCP-1) is up-regulated in the tubulointerstitium and in the glomeruli in many human and experimental kidney disorders. We investigated the localization of MCP-1 expression in a rat model of progressive kidney failure. Male Wistar rats were subjected to subtotal nephrectomy (n = 30) or sham surgery (n = 30). Immunohistochemistry with immunoelectron microscopy and in situ hybridization were used to examine the expression of MCP-1 protein and messenger ribonucleic acid (mRNA) in the kidney, respectively. MCP-1 protein and mRNA were hardly detected in both glomeruli and tubulointerstitium of control rats. However, in the rats subjected to nephrectomy, MCP-1 expression was increased in the tubular cells of the remnant kidney, accompanied by significant macrophage infiltration. MCP-1 was observed mainly in the proximal tubular cells and only weakly in distal tubular cells. No significant expression of MCP-1 protein or mRNA was noted in the glomeruli. Immunoelectron microscopy showed the presence of MCP-1 in the rough endoplasmic reticulum of proximal tubular cells, confirming that MCP-1 is produced in proximal tubular cells. MCP-1 was also observed in endocytic vesicles adjacent to the brush border of proximal tubular cells, suggesting incorporation of MCP-1 from the tubular lumen. Our findings indicate localized expression of MCP-1 in proximal tubular cells in the remnant kidney and suggest that MCP-1 in proximal tubular cells is involved in tubulointerstitial damage in chronic kidney failure associated with glomerular hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CCL2 / genetics*
  • Disease Models, Animal
  • Disease Progression
  • Kidney Tubules / pathology
  • Kidney Tubules / physiopathology*
  • Kidney Tubules / ultrastructure
  • Male
  • Microscopy, Immunoelectron
  • Nephrectomy
  • Rats
  • Rats, Wistar
  • Renal Insufficiency / genetics*
  • Renal Insufficiency / pathology
  • Urothelium / pathology
  • Urothelium / physiopathology*
  • Urothelium / ultrastructure


  • Chemokine CCL2