Renal Fibrosis and Glomerulosclerosis in a New Mouse Model of Diabetic Nephropathy and its Regression by BMP-7 and Advanced Glycation End-Product Inhibitors.

@article{citeulike:1386932, abstract = {Diabetic nephropathy is currently the most common cause of end-stage renal disease (ESRF) in the western world. A mouse model for diabetic nephropathy that encompasses the salient features of this disease in the kidney is not available. Here, we report that CD1 mice, in contrast to inbred C57BL/6 and 129sv strains, develop ESRF associated with prominent tubulointerstitial nephritis and fibrosis within three months and die due to diabetic complication by 6-7 months after a single injection of streptozotocin. Histopathologic lesions observed in these mice mimic human diabetic nephropathy including glomerular hypertrophy, diffuse glomerulosclerosis, tubular atrophy, interstitial fibrosis and decreased renal excretory function. Next, we tested the therapeutic efficacy of bone morphogenic protein-7 (BMP-7) and inhibitors of advanced glycation end-products (AGE), aminoguanidine and pyridoxamine, to inhibit and regress the progression of renal disease in diabetic CD1 mice. We demonstrate that while aminoguanidine, pyridoxamine and BMP-7 significantly inhibit glomerular lesions, BMP-7 is most effective in the inhibition of tubular inflammation and tubulointerstitial fibrosis in these mice. Collectively, our results report a new mouse model for diabetic nephropathy with prominent interstitial inflammation and fibrosis and the selective inhibition of diabetic kidney disease by AGE inhibitors and BMP-7.}, address = {Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.}, author = {Sugimoto, Hikaru and Grahovac, Gordan and Zeisberg, Michael and Kalluri, Raghu }, citeulike-article-id = {1386932}, doi = {10.2337/db06-1226}, issn = {0012-1797}, journal = {Diabetes}, keywords = {animal, dn}, month = {April}, posted-at = {2008-03-22 13:08:49}, priority = {4}, title = {Renal Fibrosis and Glomerulosclerosis in a New Mouse Model of Diabetic Nephropathy and its Regression by BMP-7 and Advanced Glycation End-Product Inhibitors.}, url = {http://dx.doi.org/10.2337/db06-1226}, year = {2007} }

TY - JOUR ID - citeulike:1386932 L3 - citeulike-article-id:1386932 TI - Renal Fibrosis and Glomerulosclerosis in a New Mouse Model of Diabetic Nephropathy and its Regression by BMP-7 and Advanced Glycation End-Product Inhibitors. JF - Diabetes AD - Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215. SN - 0012-1797 N2 - Diabetic nephropathy is currently the most common cause of end-stage renal disease (ESRF) in the western world. A mouse model for diabetic nephropathy that encompasses the salient features of this disease in the kidney is not available. Here, we report that CD1 mice, in contrast to inbred C57BL/6 and 129sv strains, develop ESRF associated with prominent tubulointerstitial nephritis and fibrosis within three months and die due to diabetic complication by 6-7 months after a single injection of streptozotocin. Histopathologic lesions observed in these mice mimic human diabetic nephropathy including glomerular hypertrophy, diffuse glomerulosclerosis, tubular atrophy, interstitial fibrosis and decreased renal excretory function. Next, we tested the therapeutic efficacy of bone morphogenic protein-7 (BMP-7) and inhibitors of advanced glycation end-products (AGE), aminoguanidine and pyridoxamine, to inhibit and regress the progression of renal disease in diabetic CD1 mice. We demonstrate that while aminoguanidine, pyridoxamine and BMP-7 significantly inhibit glomerular lesions, BMP-7 is most effective in the inhibition of tubular inflammation and tubulointerstitial fibrosis in these mice. Collectively, our results report a new mouse model for diabetic nephropathy with prominent interstitial inflammation and fibrosis and the selective inhibition of diabetic kidney disease by AGE inhibitors and BMP-7. KW - animal KW - dn AU - Sugimoto, Hikaru AU - Grahovac, Gordan AU - Zeisberg, Michael AU - Kalluri, Raghu PY - 2007/04/24/ UR - http://dx.doi.org/10.2337/db06-1226 ER -