Knockdown of Stat3 activity in vivo prevents diabetic glomerulopathy.
Knockdown of Stat3 activity in vivo prevents diabetic glomerulopathy.
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DOI：
10.1038/ki.2009.98
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发表时间：
2009-07
影响因子：
19.6
通讯作者：
He, John Cijiang
中科院分区：
文献类型：
--
作者：
Lu, Ting-Chi;Wang, Zhao-Hui;Feng, Xiaobei;Chuang, Peter Y.;Fang, Wei;Shen, Yuhong;Levy, David E.;Xiong, Huabao;Chen, Nan;He, John Cijiang
最近的研究表明，Stat 3，一个转录因子介导的细胞因子信号，在糖尿病肾病的发病机制中起着至关重要的作用。完整的Stat 3基因敲除是胚胎致死的;因此，我们将Stat 3 +/-小鼠与缺乏完整Stat 3活性的Stat 3突变小鼠（SA/SA）杂交。该策略产生了Stat 3SA/-小鼠（25%活性）和Stat 3SA/+小鼠（75%活性），使用链脲佐菌素使其患糖尿病，以确定Stat 3在糖尿病肾病中的作用。虽然这两组小鼠之间的肾小球数量没有差异，但糖尿病SA/-小鼠的蛋白尿、系膜扩张、肾小球细胞增殖和巨噬细胞浸润显著少于糖尿病SA/+小鼠。Stat 3活性的降低并不影响诱导糖尿病后观察到的肾小球超滤，因为它在两组小鼠中增加到相同的程度。与糖尿病SA/-小鼠相比，糖尿病SA/+小鼠肾小球中Stat 3的磷酸化显著增加。与糖尿病SA/+小鼠相比，从糖尿病SA/-小鼠分离的肾小球中发现炎症标志物IL-6、MCP-1和活化的NF-κB; IV型胶原、TGF-β和ICAM-1 mRNA;或IV型胶原和TGF-β蛋白的表达均显著减少。我们的研究表明，Stat 3在DN早期炎症和异常基质合成的调节中起着关键作用。
Recent studies suggest that Stat3, a transcription factor that mediates cytokine signaling, plays a critical role in the pathogenesis of diabetic nephropathy. Complete Stat3 gene knockout is embryonic lethal; therefore, we crossed Stat3+/– mice with Stat3 mutant mice (SA/SA) that lack full Stat3 activity. This strategy generated Stat3SA/– mice (25% activity) and Stat3SA/+ mice (75% activity), which were made diabetic using streptozotocin in order to define the role of Stat3 in diabetic kidney disease. While the glomerular number was not different between these two groups of mice, the diabetic SA/– mice had significantly less proteinuria, mesangial expansion, glomerular cell proliferation, and macrophage infiltration than the diabetic SA/+ mice. The reduction in Stat3 activity did not affect glomerular hyperfiltration seen after the induction of diabetes, as it was increased to the same degree in both groups of mice. Phosphorylation of Stat3 was markedly increased in the glomeruli of diabetic SA/+ mice compared to diabetic SA/– mice. The expression of inflammatory markers, IL-6, MCP-1, and activated NF-κB; type IV collagen, TGF-β, and ICAM-1 mRNA; or type IV collagen and TGF-β protein, were all found to be significantly less in glomeruli isolated from diabetic SA/– mice, as compared with diabetic SA/+ mice. Our study shows that Stat3 plays a critical role in the regulation of inflammation and abnormal matrix synthesis at an early stage of DN.
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影响因子：
15.9
作者：
He, JCJ;Husain, M;Klotman, PE
通讯作者：
Klotman, PE
DOI：
10.1152/ajprenal.00502.2005
发表时间：
2006-07-01
影响因子：
4.2
作者：
Banes-Berceli, Amy K.;Shaw, Sean;Marrero, Mario B.
通讯作者：
Marrero, Mario B.
影响因子：
4.8
作者：
CHEN, NY;CHEN, WY;KOPCHICK, JJ
通讯作者：
KOPCHICK, JJ
DOI：
10.1152/ajprenal.1995.269.2.f266
发表时间：
1995-08-01
期刊：
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY
影响因子：
--
作者：
HE, CJ;ZALUPS, RK;STRIKER, LJ
通讯作者：
STRIKER, LJ
影响因子：
8.2
作者：
Saraheimo, M;Teppo, AM;Groop, PH
通讯作者：
Groop, PH