| Budget Amount *help |
¥3,980,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
This research project was conducted to clarify the role of hypoxia-responsive molecule and existing inflammation in the development of renal interstitial fibrosis. Induction of heme oxygenase-1 (HO-1), a well-known hypoxia-inducible molecule, attenuated renal fibrosis in rat obstructive uropathy whereas interstitial infiltration of macrophages increased unexpectedly. In contrast, T cell influx was markedly attenuated. Immunohistochemical localization of HO-1 revealed its expression in the infiltrating macrophages, suggesting that these cells may be protective to fibrosis. Erythropoietin (EPO), another hypoxia-inducible molecule, was tested in the obstructive uropathy. Although EPO increased blood hemoglobin concentration, it did not affect renal fibrosis. These results suggested that hypoxia-inducible molecules, HO-1 but not EPO has ability to attenuate renal fibrosis. Next, we examined to determine gene expression profile associated with inflammatory cell influx and also the effects of anti-inflammatory drug. For this sake, glomerular gene expression of mouse model of lupus nephritis was assessed by microarray. These glomeruli showed high expression of various chemokines and their receptors that was accompanied by marked influx of macrophages, T cells and neutrophils. Prednisolone markedly attenuated all of these responses. Taken together, it is suggested that hypoxia-inducible HO-1 is anti-fibrotic but its action on infiltrating cells depends on the species of the inflammatory cells that is in marked contrast to the action of anti-inflammatory gluco-corticoid.
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