Expression of macrophage metalloelastase (MMP-12) in podocytes of hereditary nephrotic mice (ICGN Strain)

Abstract

The Institute for Cancer Research (ICR)-derived glomerulonephritis (ICGN) mouse is a good model for renal fibrosis. In the glomeruli and tubulointerstitium of ICGN mouse kidneys, the components of the extracellular matrix (ECM) accumulated, and matrix metalloproteinases (MMPs) participated in this process. To clarify the mechanism of renal fibrosis, we investigated the expression and localization of macrophage metalloelastase (MMP-12), whose functions in kidney diseases are not fully understood, and its regulatory molecules, monocyte chemoattractive protein-1 (MCP-1) and CC chemokine receptor 2 (CCR2), in the kidneys of ICGN mice by RTPCR, Western blotting and immunohistochemical staining, respectively. Extensive expression of MMP-12 mRNA and its protein was noted in ICGN mice with progressed nephrotic syndrome. The increase in MMP-12 expression occurred predominantly in podocytes. Furthermore, MCP-1 and CCR2 were also increased in podocytes of the ICGN strain. These results suggest that the expression of MMP12 is involved in the progression of nephrotic syndrome in ICGN mice.