Identification of novel NO-regulated genes involved in inflammatory processes during renal diseases and cutaneous wound healing
S. Frank (group leader), I. Goren
Within the last few years, the role for nitric oxide (NO) as an important mediator of physiological and pathophysiological processes has become evident. Now, it is well known that NO influences gene expression in its target cells. Inflammatory processes are characterized by the presence of inducible nitric oxide synthase (iNOS), which is expressed by infiltrating immune cells and activated cells within the inflamed tissue, thus generating large amounts of NO that is released into the surrounding tissue.
Since molecular mechanisms which underlie the action of NO in normal and diseased tissue have not yet been elucidated, we were interested especially in genes which are regulated by this short-lived molecule during inflammatory processes in the kidney and during wound healing of the skin.
To address this question, we have established cell culture systems for kidney- and renal-derived cell lines. Using this in vitro system, we isolate genes that are under regulatory control of NO.
To evaluate the possible relevance of our identified NO-regulated genes for an in vivo situation, we have chosen a rat model of septic shock induced by endotoxin application (in collaboration with C. Thiemermann, William Harvey Research Institute, London) and an in vivo wound healing model in the mouse.
Supported by grants of the Deutsche Forschungsgemeinschaft (SFB 553) and the Förderung der Nachwuchswissenschaftler am Klinikum der Johann Wolfgang Goethe-Universität.