Both ERK/MAPK and TGF-Beta/Smad signaling pathways play a role in the kidney fibrosis of diabetic mice accelerated by blood glucose fluctuation.
Both ERK/MAPK and TGF-Beta/Smad signaling pathways play a role in the kidney fibrosis of diabetic mice accelerated by blood glucose fluctuation.
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ERK/MAPK 和 TGF-Beta/Smad 信号通路在血糖波动加速的糖尿病小鼠肾纤维化中发挥作用
DOI：
10.1155/2013/463740
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发表时间：
2013
影响因子：
4.3
通讯作者：
Ye X
中科院分区：
文献类型：
--
作者：
Cheng X;Gao W;Dang Y;Liu X;Li Y;Peng X;Ye X
背景。糖尿病肾病是肾纤维化的主要原因，这一观点促使我们研究了高糖条件下血糖波动（BGF）对小鼠肾脏的影响。方法。本研究建立了糖尿病和BGF动物模型。采用免疫组化、Western blot、RT-PCR检测I型胶原、基质金属蛋白酶-1 （MMP1）、金属蛋白酶抑制剂1 （TIMP1）、转化生长因子-1 （TGF-β1）、磷酸化- erk、p38、smad2/3、Akt的表达。结果。与对照组相比，BGF处理使I型胶原合成增加了两倍。BGF处理后，MMP1的表达明显降低，TIMP1的合成增强。在BGF处理的小鼠中，ERK磷酸化表现出显著的增加。此外，BGF可显著上调TGF-β1的表达。与糖尿病小鼠相比，p-smad2增加了2倍。然而，在BGF治疗后，p-AKT水平没有变化。结论。这些数据表明，BGF可以通过增加胶原生成和抑制胶原降解来加速糖尿病小鼠肾纤维化的趋势。ERK/MAPK和TGF-β/smad信号通路似乎都在血糖波动加速的肾纤维化发展中发挥作用。
Background. The notion that diabetic nephropathy is the leading cause of renal fibrosis prompted us to investigate the effects of blood glucose fluctuation (BGF) under high glucose condition on kidney in the mice. Methods. The diabetic and BGF animal models were established in this study. Immunohistochemistry, Western blot, and RT-PCR analysis were applied to detect the expression of type I collagen, matrix metalloproteinase-1 (MMP1), metalloproteinase inhibitor 1 (TIMP1), transforming growth factor beta 1 (TGF-β1), phosphorylated-ERK, p38, smad2/3, and Akt. Results. BGF treatment increased type I collagen synthesis by two times compared with the control. The expression of MMP1 was reduced markedly while TIMP1 synthesis was enhanced after BGF treatment. ERK phosphorylation exhibits a significant increase in the mice treated with BGF. Furthermore, BGF can markedly upregulate TGF-β1 expression. The p-smad2 showed 2-fold increases compared with the only diabetic mice. However, p-AKT levels were unchanged after BGF treatment. Conclusions. These data demonstrate that BGF can accelerate the trend of kidney fibrosis in diabetic mice by increasing collagen production and inhibiting collagen degradation. Both ERK/MAPK and TGF-β/smad signaling pathways seem to play a role in the development of kidney fibrosis accelerated by blood glucose fluctuation.
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DOI：
10.1152/ajprenal.00065.2005
发表时间：
2005-11-01
影响因子：
4.2
作者：
Sugaru, E;Sakai, M;Taiji, M
通讯作者：
Taiji, M
影响因子：
5.3
作者：
Quagliaro, L;Piconi, L;Ceriello, A
通讯作者：
Ceriello, A
影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Ceriello, A
DOI：
10.1161/01.atv.0000239488.05069.03
发表时间：
2006-10-01
影响因子：
8.7
作者：
Azuma, Kosuke;Kawamori, Ryuzo;Watada, Hirotaka
通讯作者：
Watada, Hirotaka