[SA-PO606] Molecular Mechanisms Underlying Mesangioproliferative Kidney Damage in a Rat Anti-thy1.1 Model of Glomerulonephritis: A Gene Expression Analysis.

Amitabha Chaudhuri, Carol Pena, Glennda Smithson, Gary Starling, Frank Spriggs, Jeffrey L. Barnes, John Chant, Loic Giot.. Preclinical/Drug Discovery, Curagen Corporation, Branford, CT; Probetex, Inc., San Antonio, TX

A variety of human nephropathies such as IgA and lupus nephritis are associated with the proliferation of mesangial cells. The aim of this study was to understand how the proliferation and activation of mesangial cells causes kidney damage. We have used the ATS-induced rat anti-thy1.1 model to define mechanisms by which mesangial cell proliferation in the glomerulus causes damage to the kidney. In this model, the maximum hypercellularity of the glomerulus is seen on day 5 followed by a period of cell death and matrix deposition. The damage starts resolving after day 14. We examined changes in gene expression at days 5, 9 and 15 in isolated glomeruli and tubules using Affymetrix arrays. A cluster analysis of genes, which were significantly upregulated indicated activation of four distinct biological processes in the glomerulus and tubules. Our molecular analysis supported that mesangial cell proliferation and activation drives inflammatory responses leading to matrix deposition and cellular damage. The findings of our gene expression data were supported by histopathological examination of rat kidneys. We conclude that the mechanisms of kidney damage operating in the rat model have characteristics of human proliferative kidney diseases, and that human ortholog of rat genes identified in this study will provide anchor points to examine kidney damage in human mesangioproliferative glomerulonephritis.

Date: Saturday, October 30, 2004 10:00 AM

Session Info: Poster: Genomics (10:00 AM - 12:00 PM) Poster Board Number: SA-PO606

Room: Halls 2-4

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