CORE--RENAL INJURY MODEL

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Description: (Adapted from the application) The overall objective of this Core is to develop and define in vivo experimental systems which can test how the protein-protein interactions which are the main focus of the individual projects at the cellular level are disrupted in the whole kidney of the intact animal during ischemic and hypoxic injury and the mechanisms by which normal renal structure (and function) is restored during recovery. While it is important to understand how individual cell membrane proteins interact with specific cytoskeletal elements on a molecular level and how these interactions are disrupted during ATP depletion, it is necessary to analyze these changes at different levels of organization including the cellular, organ and whole animal to fully understand their pathobiological importance. This principle has been clearly demonstrated in so called knockout experiments where more often than not the result at the whole animal level is less dramatic than anticipated, demonstrating a level of complexity and redundancy which cannot be appreciated fully in isolated cell culture systems. In an in vivo model both cellular and systemic processes are needed to achieve full functional physiologic recovery and to understand interrelationships between vascular and epithelial structures, growth factors and cytokines and hemodynamic and cellular alterations which can influence the nature of response to injury and recovery. Thus, animal models provide the only way that the integration, relative importance and hierarchy of the specific molecular and cellular responses that occur in ischemic renal injury and in the critical components of recovery can be determined. The provision of animal models by the core will provide a center for the application of basic cell and molecular biologic studies to the clinical problem of acute renal failure.