Renal injury is a well-documented consequence of shock wave lithotripsy (SWL) that for some patients (particularly the young and the elderly( may poe a significant health risk. How SWL causes tissue damage is not known. We do not known what physical mechanisms of shock wave (SW) impact are involved, and we do not know the cellular mechanisms of response to SW trauma. Our main objective is to determine how SWL causes tissue damage, and how the trauma of cellular injury leads to permanent changes in the kidney. Project 1 continues to make excellent progress in understanding the effects of SWL in vivo, but the complexity of the kidney makes the definition of specific cause-and-effect relationships difficult. Similarly, Projects 3 & 4 address the physical mechanisms of SW action, but SW interactions with the kidney are very complex. Project 2 provides a bridge to simplify these problems by using defined, in vitro biological systems. This will be a highly interactive collaborative investigation involving all projects of the SWL-PPG. Our approach is to use cultured cells, tissue slices and isolated in vitro systems to model shock wave response to the kidney tubular epithelium and vascular endothelium. We will: . assess for SWL activation of gene expression for transcription factors (cmyc, cfos, erg-1), heat shock proteins (hsp-70) and fibrogenic cytokines (TGF-b1, IL-1, TNF) involved in SW trauma and the SW-induced inflammatory response that leads to scar formation. . determine how conditions of SW treatment influence injury and affect cell response to subsequent trauma. . determine the role of cavitation and shear in cell damage.
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