Bedeutung des "kidney injury molecule-1" für die Zell-Matrix-Wechselwirkung von renalen tubulären Epithelzellen nach ischämischer Nierenschädigung (Role of "kidney injury molecule-1" in cell-matrix interaction of renal tubular epithelial cells after ische

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Ischemic and toxic forms of acute renal failure as well acute tubular necorsis in kidney transplantation are important causes of morbidity and mortality in hospitalized patients. Regeneration of the tubular epithelium which is injured in these diseases is cirtically regulated by the interaction of epithelial cells with the extracellular matrix and the basement membrane. As a molecule which appears to play a critical role in the processes of tubular injury and repair we identified "kidney injury molecule-1" (KIM-1) which is a cell membrane glycoprotein containing an immunoglobulin-like domain and a mucin domain in the extracellular portion. KIM-1 is strongly upregulated in vivo in proximal tubular epithelial cells where most of the damage and repair occurs. Based on previous results we propose that KIM-1 is an anti-adhesion molecule which changes interaction of epithelial cells with the extracellular matrix and promotes scattering of epithelial cells expressing KIM-1. The aim of this project is to further examine the functional role of KIM-1 in the processes of adhesion, polarization, de-differentiation, proliferation, and migration of cultured tubular epithelial cells. Furthermore, we will characterize the expression of KIM-1 during the course of kidney transplantation in humans and evaluate KIM-1 expression as prognostic marker for renal allograft survival. The results of this study will help us to understand the role of KIM-1 in the pathogenesis of acute renal failure as well as renal transplant failure and will ultimately lead to new therapeutic and diagnostic approaches in renal disease.