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

肾移植中缺血性和中毒性急性肾功能衰竭以及急性肾小管坏死是住院患者发病和死亡的重要原因。在这些疾病中受损的小管上皮的再生是由上皮细胞与细胞外基质和基底膜的相互作用循环调节的。作为一个在肾小管损伤和修复过程中起关键作用的分子，我们发现了“肾损伤分子-1”（KIM-1），它是一种细胞膜糖蛋白，在细胞外部分含有免疫球蛋白样结构域和粘蛋白结构域。KIM-1在体内近端小管上皮细胞中被强烈上调，大部分损伤和修复发生在近端小管上皮细胞中。基于先前的研究结果，我们提出KIM-1是一种抗粘附分子，它改变上皮细胞与细胞外基质的相互作用，促进表达KIM-1的上皮细胞的散射。本项目旨在进一步研究KIM-1在培养的小管上皮细胞的粘附、极化、去分化、增殖和迁移过程中的功能作用。此外，我们将表征人类肾移植过程中KIM-1的表达，并评估KIM-1表达作为同种异体肾移植存活的预后指标。这项研究的结果将有助于我们了解KIM-1在急性肾功能衰竭和肾移植衰竭的发病机制中的作用，并最终导致肾脏疾病的新的治疗和诊断方法。

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.