Expression and regulation od PC-cell derived growth factor in a rat model of progressive renal disease *
The PC-cell derived growth factor（PCDGF）was originally purified from teratoma tumor cells and has multiple physiological actions on cell growth, migration, and transformation. The expression of PCDGF seems to be well regulated under normal conditions but little is known about the regulatory mechanisms under various pathological conditions. Progressive renal diseases are etiologically multifactorial and can result in irreversible renal failure. In this study, we investigated the link between PCDGF and progressive renal disease using the remnant kidney, a suitable model for the study of progressive renal disease. The presence of high PCDGF mRNA and protein levels correlated with renal dysfunction. Immunohistochemical studies showed PCDGF expression in the kidneys of sham-operated rats, which was strong in the medulla but weak in the cortex. However, in the remnant kidneys, PCDGF expression was markedly increased in tubular epithelial cells of atrophic nephrons in the cortex at 8 weeks, which was also confirmed by in situ hybridization. Furthermore, PCDGF expression further increased with wide expansion at 16 weeks. Next, we examined the effect of hypoxia on PCDGF expression in tubular epithelial cells since chronic renal hypoxemia is considered a pathogenic mechanism of progressive renal disease. Exposure of cultured human renal epithelial cells to 24-hr hypoxia（５％ and １％ oxygen）increased both the mRNA and protein levels of PCDGF in these cells. Our results suggest the involvement of PCDGF in the progression of renal diseases through abnormal overexpression in cortical tubular epithelial cells in response to chronic renal hypoxemia.（Accepted on October 17，2007)
