HGM2002 Poster Abstracts: 8. Disease Mechanisms
POSTER NO: 441
Gene expression profiling analysis shows possible signal transduction pathways leading to cardiac structural changes in left ventricular hypertrophy of renal failure
1Christian Maercker, 1Christiane Rutenberg, 2Eberhard Ritz, 3Gerhard Mall, 4Kerstin Amann
By gene expression profiling, we have investigated signaling molecules which obviously take in a major role in re-organizing the cytoskeleton, the extracellular matrix, and the capillary density in hearts of rats with renal failure. Male Sprague-Dawley rats, which were subjected to sub-total nephrectomy (SNX), served as a model system for a gene expression profiling analysis. Poly(A)+ RNA from the hearts of SNX animals and from sham-operated rats (SHAM) as a control, were labeled and hybridized with Rat UniGene filters containing about 27.000 gene and EST sequences (Bento Soares, Univ. of Iowa). Phosphoimaging and software analysis revealed substantial changes in gene expression in SNX animals compared to SHAM: Not only integrin a1 and b1 as central players, but also genes downstream of the integrin signaling pathway, like calreticulin, rac protein kinase a, rho A and rho B have been shown to be up-regulated in SNX animals. Rho protein again, might be causal for the stimulation of the expression different enzymes of the phosphatidylinositol pathway up to cardiac dynein and actin, which also has been shown by our experiments. Therefore, the gene expression profiling experiments discussed here not only allow us to describe genes involved in activation and expansion of the non-vascular interstitial tissue in uraemic animals, like timp3, tgf-b1, osteonectin, paxillin, and laminin a1, and linker molecules like plectin, catenin, cadherin and ICAM. These experiments also make it possible to find central signaling molecules responsible for the pathomechanisms involved in cardiac structural changes upon renal failure.
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