Gene expression in Podocytes under Stretch Stress Conditions

Several renal diseases are associated with increased intraglomerular capillary pressure, this results in stretch tension stress that injures cells of the kidney`s filtration apparatus. The cellular response to tension injury will be studied by microarrays. Genes that negatively influence podocyte-vitality will be blocked by antisense therapy. Podocytes are a main component of the renal filtration apparatus. Injury and distruction of podocytes is common to several renal diseases. Common to all glomerular diseases is an increase of intraglomerular capillary pressure that induces stretch tension stress and subsequently podocyte injury. This insult is followed by podocyte death. Mature podocytes are highly differentiated and unable to proliferate, and thus lost cells are not replaced. Aim of this proposal is to simulate tension stress on podocytes in vitro and to analyse the cell`s response by microarrays. We seek to identify genes involved in the response of podocytes to tension stress injury. In a further experiment these genes should be inhibited by antisense molecules. The effect of this blockade will also be described by microarray analysis. The insight gained by these eperiments will be the basis for early diagnosis of glomerular diseases and thus help to slow progression of native and transplant renal disease.