Acute tubular necrosis as a result of nephrotoxic damage by environmental chemicals has been a topic of interest for several decades. This is primarily due to evidence that the kidney is a major target for toxicant- induced damage. Investigators have characterized the mechanism(s) of toxicity for a variety of environmental nephrotoxic agents. However, little information is available with regards to the biochemical/molecular events which follow acute tubular injury. Toxicant-induced acute tubular necrosis is followed by a regenerative hyperplasia of renal tubular epithelial cells. The regenerative process can develop to a more chronic degenerative lesion. Furthermore, recent evidence suggests that tissue wounding and chronic repair may be involved in the ability of non- genotoxic carcinogens to cause renal cancer. Currently, mediators responsible for regenerative and chronic degenerative processes have not been elucidated. It is also unknown whether mediators involved in chronic tissue repair are expressed during renal tumorigenesis. Investigators have demonstrated that growth factors are involved in the regenerative repair response following xenobiotic-induced toxic insult. Growth factors have also been implicated as mediators of progressive renal disease and factors which may promote the manifestation of renal cancer. The goal of the proposed studies is to determine the role of FGFs in the regenerative repair, chronic degenerative disease and renal cancer processes. In addition, these studies will attempt to establish a biochemical link between each disease state.
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| Liu, H; Bowes 3rd, R C; van de Water, B et al. (1997) Endoplasmic reticulum chaperones GRP78 and calreticulin prevent oxidative stress, Ca2+ disturbances, and cell death in renal epithelial cells. J Biol Chem 272:21751-9 |
