Significance and molecular mechanisms of natriuretic peptide family in the protection from renal dysfunction

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(1) Pathohysioloical significance of natriuretic peptide family in the animal models of renal diseasesWe have established animal models of renal diseases (anti-glomerular basement membrane antibody glomerulonephritis ; anti-GBM antibody GN, STZ diabetic nephropathy model and unilateral ureteral obstruction hydronephrosis model) in rats and mice, and elucidated the localization of natriuretic peptide family by Nothern blot analysis and immunohistochemical method using anti-ANP, BNP, CNP monoclonal antibodies. The results indicated that these peptides may be the parameter of renal dysfunction.(2) Study on the cross-talk of natriuretic peptide system and renin-angiotensin systemNatriuretic peptide system is thought to antagonize renin-angiotensin system. To clarify the intra-cellular mechanism of natriuretic psptides, we have investigated the induction of TGF-β, CTGF and extra-cellular matrix using cultured mesangial cells. We have also succeeded the cloning of rat CTGF and raised the specific antibody.(3) Kidney protection in BNP transgenic mouse and its molecular mechanismWe have established the 5/6 nephrecomized model using BNP transgenic mice which show the activation of renal renin-angiotensin system. Using this animal model, significant increase in size of glomeruli is observed in the control rats, whereas in the BNP transgenic mice, such glomerular change is not observed, showing that excessive BNP may work as kidney protection. Using this BNP transgenic mice, we have further established the unilateral ureteral obstruction hydronephrosis model and anti-GBM antibody GN model. With these models, we have shown the kidey-protection of BNP, at least in part, by the immunological mechanism.