Thioredoxin-interacting protein gene expression via MondoA is rapidly and transiently suppressed during inflammatory responses.
Thioredoxin-interacting protein gene expression via MondoA is rapidly and transiently suppressed during inflammatory responses.
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DOI：
10.1371/journal.pone.0059026
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Muta T
中科院分区：
文献类型：
--
作者：
Kanari Y;Sato Y;Aoyama S;Muta T
尽管越来越多的证据表明许多炎症基因是由核因子-κB和其他转录因子的激活诱导的，但对被促炎刺激抑制的基因却知之甚少。在这里，我们表明，硫氧还蛋白相互作用蛋白（Txnip）的表达显着抑制后，在小鼠和人巨噬细胞与脂多糖刺激的mRNA和蛋白质水平。除了脂多糖（Toll样受体4配体）之外，用其它Toll样受体配体（如CpG DNA）刺激也抑制Txnip表达。不仅Toll样受体配体，而且其他促炎刺激物，如白细胞介素-1 β和肿瘤坏死因子-α在成纤维细胞中也引起类似的反应。通过脂多糖抑制Txnip伴随着细胞核中葡萄糖敏感转录因子MondoA的减少和MondoA：Mlx复合物的解离，所述复合物结合至未刺激细胞中Txnip启动子中的碳水化合物响应元件。在2-脱氧葡萄糖存在下，脂多糖介导的核MondoA减少被抑制。此外，阻断甘油醛-3-磷酸脱氢酶碘乙酸减轻抑制Txnip mRNA的脂多糖，表明葡萄糖代谢产物的参与调节。由于Txnip涉及葡萄糖代谢的调节，因此该观察结果将炎症反应和代谢调节联系起来。
Whereas accumulating evidence indicates that a number of inflammatory genes are induced by activation of nuclear factor-κB and other transcription factors, less is known about genes that are suppressed by proinflammatory stimuli. Here we show that expression of thioredoxin-interacting protein (Txnip) is dramatically suppressed both in mRNA and protein levels upon stimulation with lipopolysaccharide in mouse and human macrophages. In addition to lipopolysaccharide, a Toll-like receptor 4 ligand, stimulation with other Toll-like receptor ligands such as CpG DNA also suppressed Txnip expression. Not only the Toll-like receptor ligands, but also other proinflammatory stimulators, such as interleukin-1β and tumor necrosis factor-α elicited the similar response in fibroblasts. Suppression of Txnip by lipopolysaccharide is accompanied by a decrease of the glucose sensing transcription factor MondoA in the nuclei and dissociation of the MondoA:Mlx complex that bound to the carbohydrate-response elements in the Txnip promoter in unstimulated cells. Lipopolysaccharide-mediated decrease of nuclear MondoA was inhibited in the presence of 2-deoxyglucose. Furthermore, blockage of glyceraldehyde-3-phosphate dehydrogenase by iodoacetate alleviated the suppression of Txnip mRNA by lipopolysaccharide, suggesting the involvement of glucose-metabolites in the regulation. Since Txnip is implicated in the regulation of glucose metabolism, this observation links between inflammatory responses and metabolic regulation.
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影响因子：
4.8
作者：
Shao, Weijuan;Yu, Zhiwen;Jin, Tianru
通讯作者：
Jin, Tianru
影响因子：
4.8
作者：
Ge, Qiang;Nakagawa, Tsutomu;Uyeda, Kosaku
通讯作者：
Uyeda, Kosaku
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
4.8
作者：
Patwari, Parth;Chutkow, William A.;Lee, Richard T.
通讯作者：
Lee, Richard T.
TXNIP调节人类的外周葡萄糖代谢。
影响因子：
15.8
作者：
Parikh, Hemang;Carlsson, Emma;Chutkow, William A.;Johansson, Lovisa E.;Storgaard, Heidi;Poulsen, Pernille;Saxena, Richa;Ladd, Christine;Schulze, P. Christian;Mazzini, Michael J.;Jensen, Christine Bjorn;Krook, Anna;Bjornholm, Marie;Tornqvist, Hans;Zierath, Juleen R.;Ridderstrale, Martin;Altshuler, David;Lee, Richard T.;Vaag, Allan;Groop, Leif C.;Mootha, Vamsi K.
通讯作者：
Mootha, Vamsi K.