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

Abstract

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. (J Lab Clin Med 2002;140:43-51)