|Bone morphogenic protein-7 (BMP-7), a novel therapy for diabetic nephropathy|
|Wang, S1; Chen, Q1; Simon, TC1; Strebeck, F1; Chaudhary, L1; Morrissey, J1; Liapis, H1; Klahr, S1; Hruska, KA1|
|关键词||Bmp-7 Diabetic Nephropathy Chronic Kidney Disease|
|WOS标题词||Science & Technology|
|类目[WOS]||Urology & Nephrology|
|研究领域[WOS]||Urology & Nephrology|
|关键词[WOS]||GROWTH-FACTOR-BETA ; CONVERTING ENZYME-INHIBITION ; EPITHELIAL TRANSFORMATION ; METANEPHRIC MESENCHYME ; URETERAL OBSTRUCTION ; DEVELOPING KIDNEY ; GENE-EXPRESSION ; RENAL FIBROSIS ; MESSENGER-RNA ; RATS|
Background. Bone morphogenic protein-7 (BMP-7), an essential developmental renal morphogen, is a secreted differentiation factor of the adult collecting duct. It activates receptors in the collecting duct, distal nephron, proximal tubule, and glomerulus. BMP-7 is therapeutic in tubulointerstitial nephritis raising the question of broader efficacy in chronic kidney disease (CKD).
Methods. Diabetes was induced in 200 g rats by a single dose of streptozotocin. After 16 weeks, glomerular hypertrophy and proteinuria were established, and therapy with BMP-7 (10, 30, or 100 mug/kg intravenously twice a week), enalapril (20 mg/kg), or vehicle was begun and continued until 32 weeks. Kidney weight, glomerular filtration rate (GFR), urine albumin excretion, blood pressure, pathology, and BMP-7 expression were measured.
Results. Diabetic vehicle-treated rats developed renal insufficiency by 32 weeks (GFR, 0.34+/-0.02 mL/min/100 g body weight vs. 0.55+/-0.02 in normal). In the diabetic BMP-7 high-dose-treated rats, GFR was preserved (0.70+/-0.08, P<0.01 vs. vehicle), and higher than diabetic enalapril-treated rats (0.58+/-0.06). Kidney weights of vehicle-treated animals were not affected, but were reduced in all of the treatment groups (P<0.001). Proteinuria was reversed to normal by BMP-7 in a dose-dependent manner. The reduction in proteinuria by the intermediate dose of BMP-7 was similar to the effect of enalapril therapy. Glomerular area and interstitial volume were significantly decreased in the BMP-7 and enalapril-treated animals. Glomerular sclerosis was prevented by BMP-7 therapy more effectively than by enalapril. Enalapril controlled hypertension throughout the course of therapy while BMP-7 did not affect blood pressure until the final 4 weeks of therapy. Diabetic vehicle-treated rats lost BMP-7 expression in the kidney. BMP-7 and enalapril therapy restored BMP-7 expression at high levels.
Conclusion. BMP-7 partially reversed diabetic-induced kidney hypertrophy, restoring GFR, urine albumin excretion, and glomerular histology toward normal. Restoration of BMP-7 expression was associated with a successful repair reaction and a reversal of the ill-fated injury response.
|作者单位||1.Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA|
2.Beijing Med Univ, Div Renal, Hosp 3, Beijing, Peoples R China
3.Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
4.Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA
|Wang, S,Chen, Q,Simon, TC,et al. Bone morphogenic protein-7 (BMP-7), a novel therapy for diabetic nephropathy[J]. KIDNEY INTERNATIONAL,2003,63(6):2037-2049.|
|APA||Wang, S.,Chen, Q.,Simon, TC.,Strebeck, F.,Chaudhary, L.,...&Hruska, KA.(2003).Bone morphogenic protein-7 (BMP-7), a novel therapy for diabetic nephropathy.KIDNEY INTERNATIONAL,63(6),2037-2049.|
|MLA||Wang, S,et al."Bone morphogenic protein-7 (BMP-7), a novel therapy for diabetic nephropathy".KIDNEY INTERNATIONAL 63.6(2003):2037-2049.|