Bone morphogenic protein-7 (BMP-7), a novel therapy for diabetic nephropathy
Bone morphogenic protein-7 (BMP-7), a novel therapy for diabetic nephropathy
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DOI：
10.1046/j.1523-1755.2003.00035.x
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发表时间：
2003-06-01
影响因子：
19.6
通讯作者：
Hruska, KA
中科院分区：
文献类型：
--
作者：
Wang, S;Chen, Q;Hruska, KA
背景骨形态发生蛋白-7（BMP-7）是一种重要的肾脏发育形态原，是成年集合管分泌的分化因子。激活集合管、远端肾单位、近端小管和肾小球中的受体。BMP-7在肾小管间质性肾炎中是治疗性的，提出了在慢性肾脏病（CKD）中更广泛的疗效的问题。通过单剂量链脲佐菌素在200 g大鼠中诱导糖尿病。16周后，建立肾小球肥大和蛋白尿，开始用BMP-7（10、30或100 μ g/kg，每周静脉注射两次）、依那普利（20 mg/kg）或赋形剂治疗，并持续至32周。观察各组大鼠肾脏重量、肾小球滤过率（GFR）、尿白蛋白排泄量、血压、肾脏病理及BMP-7表达。糖尿病载体治疗的大鼠在32周时出现肾功能不全（GFR，0.34+/-0.02 mL/min/100 g体重vs. 0.55+/-0.02正常）。在糖尿病BMP-7高剂量治疗的大鼠中，GFR保持不变（0.70+/-0.08，P
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