Increased renal production of transforming growth factor-beta(1) in patients with type II diabetes

Increased renal production of transforming growth factor-beta(1) in patients with type II diabetes
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DOI:
10.2337/diabetes.46.5.854
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发表时间:
1997-05-01
期刊:
影响因子:
7.7
通讯作者:
Weisberg, LS
Weisberg, LS
中科院分区:
医学1区
文献类型:
--
作者:
Sharma, K;Ziyadeh, FN;Weisberg, LS

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糖尿病肾病是I型或II型糖尿病患者的常见并发症。糖尿病肾病的发病机制被认为涉及代谢和血管因素,导致肾小球系膜基质的慢性积聚。在这种情况下,转化生长因子-β(TGF-β)和内皮素可能有助于这些过程。为了确定糖尿病患者是否表现出增加的TGF-β和内皮素,主动脉,肾静脉和尿液中这些因素的水平进行了测量,在14例II型糖尿病患者和11例非糖尿病患者进行选择性心导管插入术。测量所有患者的肾血流量,以计算整个肾脏的净质量平衡。糖尿病患者肾组织中免疫反应性TGF-β 1的净生成量为830 ± 429 ng/min,而非糖尿病患者肾组织中循环TGF-β 1的净提取量为-3479 ± 1010 ng/min,P < 0.001。与非糖尿病患者相比,糖尿病患者尿液中TGF-β的生物测定水平也显著升高(分别为2.435 +/- 0.385和0.569 +/- 0.190 ng/mg肌酐; P < 0.001)。糖尿病患者肾脏免疫反应性内皮素的产生并没有显著增加。总之,II型糖尿病与肾脏TGF-β的净生成增加有关(1),而非糖尿病患者则表现出循环TGF-β的净肾脏提取(1)。肾脏TGF-β产生增加可能是糖尿病肾病的重要表现。
Diabetic nephropathy is a common complication in patients with either type I or type II diabetes. The pathogenesis of diabetic nephropathy is thought to involve both metabolic and vascular factors leading to chronic accumulation of glomerular mesangial matrix. In this context, both transforming growth factor-beta (TGF-beta) and endothelin may contribute to these processes. To determine if diabetic patients demonstrate increased renal production of TGF-beta and endothelin, aortic, renal vein, and urinary levels of these factors were measured in 14 type II diabetic patients and 11 nondiabetic patients who were undergoing elective cardiac catheterization. Renal blood flow was measured in all patients to calculate net mass balance across the kidney. Diabetic patients demonstrated net renal production of immunoreactive TGF-beta(1) (830 +/- 429 ng/min [mean +/- SE]), whereas nondiabetic patients demonstrated net renal extraction of circulating TGF-beta(1) (-3479 +/- 1010 ng/min, P < 0.001). Urinary levels of bioassayable TGF-beta were also significantly increased in diabetic patients compared with nondiabetic patients (2.435 +/- 0.385 vs. 0.569 +/- 0.190 ng/mg creatinine, respectively; P < 0.001). Renal production of immunoreactive endothelin was not significantly increased in diabetic patients. In summary, type II diabetes is associated with enhanced net renal production of TGF-beta(1), whereas nondiabetic patients exhibit net renal extraction of circulating TGF-beta(1). Increased renal TGF-beta production may be an important manifestation of diabetic kidney disease.