Senescence marker protein-30/gluconolactonase deficiency exacerbates diabetic nephropathy through tubular injury in a mouse model of type 1 diabetes.
Senescence marker protein-30/gluconolactonase deficiency exacerbates diabetic nephropathy through tubular injury in a mouse model of type 1 diabetes.
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DOI：
10.1111/jdi.12252
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发表时间：
2015-01
影响因子：
3.2
通讯作者：
Hasegawa G
中科院分区：
文献类型：
--
作者：
Okada H;Senmaru T;Fukui M;Kondo Y;Ishigami A;Maruyama N;Obayashi H;Yamazaki M;Nakamura N;Hasegawa G
衰老标志蛋白30（SMP 30）在肾近曲小管细胞中大量表达，但其表达随着年龄的增长而降低。先前的研究表明，SMP 30表达减少可能导致与衰老相关的细胞功能恶化和组织损伤。在本研究中，我们研究了SMP 30缺乏在糖尿病肾病发病机制中的作用。在7周龄的雄性SMP 30敲除小鼠（KO）和野生型小鼠中使用链脲佐菌素诱导糖尿病。将维生素C添加到饮用水中以防止KO小鼠中的维生素C缺乏症。诱导糖尿病后12周处死小鼠。与野生型小鼠相比，非糖尿病KO小鼠中近端小管损伤的尿液生物标志物显著增加。此外，SMP 30缺失显著加重了糖尿病诱导的肾小管损伤。形态学分析显示皮质肾小管间质纤维化面积与肾小管损伤程度之间存在联系。然而，SMP 30缺失并不影响系膜扩张。肾小管损伤与缺氧诱导因子-1 α的积累和缺氧诱导因子-1 α靶向基因表达增加有关。SMP 30缺失引发氧化应激;然而，它不会加剧糖尿病小鼠中观察到的氧化应激。相反，肾小管炎症仅在糖尿病小鼠中与SMP 30缺失相关。基于这些证据，我们得出结论，SMP 30缺乏加重糖尿病小鼠近端小管损伤。随着年龄的增长，SMP 30的降低可能导致各种慢性肾脏疾病（包括糖尿病肾病）的发病率增加。
Senescence marker protein-30 (SMP30) is abundantly expressed in renal proximal tubule cells, but its expression decreases with age. Previous studies have shown that reduced SMP30 expression could contribute to aging-associated deterioration of cellular function and tissue injury. In the present study, we investigated the effects of SMP30 deficiency on the pathogenesis of diabetic nephropathy. Diabetes was induced using streptozotocin in male SMP30 knockout mice (KO) and wild-type mice at 7 weeks-of-age. Vitamin C was added to the drinking water to prevent vitamin C deficiency in KO mice. The mice were killed 12 weeks after the induction of diabetes. Urinary biomarkers for proximal tubule damage were significantly increased in non-diabetic KO mice compared with wild-type mice. Furthermore, diabetes-induced tubular damage was significantly exacerbated by SMP30 deletion. Morphological analysis showed a link between cortical tubulointerstitial fibrosis area and the degree of tubular damage. However, SMP30 deletion did not affect mesangial expansion. Tubular injury was associated with accumulation of hypoxia-inducible factor-1α and increased hypoxia-inducible factor-1α targeted gene expression. SMP30 deletion initiated oxidative stress; however, it did not exacerbate the oxidative stress seen in diabetic mice. In contrast, tubular inflammation was associated with SMP30 deletion only in diabetic mice. Based on this evidence, we concluded that SMP30 deficiency exacerbates proximal tubule injury in diabetic mice. Decreased SMP30 could contribute to the increased incidence of various chronic kidney diseases, including diabetic nephropathy, with age.
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DOI：
10.1006/bbrc.1998.9327
发表时间：
1998-09-18
影响因子：
3.1
作者：
Fujita, T;Inoue, H;Maruyama, N
通讯作者：
Maruyama, N
DOI：
10.1164/rccm.200511-1816oc
发表时间：
2006-09-01
影响因子：
24.7
作者：
Sato, Tadashi;Seyama, Kuniaki;Ishigami, Alkihito
通讯作者：
Ishigami, Alkihito
影响因子：
2
作者：
Ishii, K;Tsubaki, T;Akita, M
通讯作者：
Akita, M
影响因子：
6.2
作者：
Kiss, E;Adams, J;Wagner, J
通讯作者：
Wagner, J
影响因子：
13.2
作者：
Coresh, J;Astor, BC;Levey, AS
通讯作者：
Levey, AS