Interferon-γ suppresses intestinal epithelial aquaporin-1 expression via Janus kinase and STAT3 activation.
Interferon-γ suppresses intestinal epithelial aquaporin-1 expression via Janus kinase and STAT3 activation.
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干扰素-γ 通过 Janus 激酶和 STAT3 激活抑制肠上皮水通道蛋白-1 表达。
DOI：
10.1371/journal.pone.0118713
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
MacNaughton WK
中科院分区：
文献类型：
--
作者：
Dicay MS;Hirota CL;Ronaghan NJ;Peplowski MA;Zaheer RS;Carati CA;MacNaughton WK
炎症性肠病与电解质和水运输失调以及由此引起的腹泻有关。水通道蛋白是跨膜蛋白，在肠上皮细胞中充当水通道。我们研究了炎症细胞因子干扰素-γ（炎症性肠病的主要参与者）对小鼠结肠上皮细胞系 CMT93 中水通道蛋白-1 表达的影响。将 CMT93 单层暴露于 10 ng/mL 干扰素-γ 和水通道蛋白-1 mRNA，并分别通过实时 PCR 和蛋白质印迹测量蛋白表达。在其他实验中，CMT93 细胞在用干扰素-γ 处理之前，用抑制剂预处理或用 siRNA 转染，以阻断 Janus 激酶、STAT 1 和 3 或干扰素调节因子 2 的作用。干扰素-γ 降低小鼠肠上皮细胞中水通道蛋白-1 的表达，其方式不依赖于经典的 STAT1/JAK2/IRF-1 通路，而是依赖于另一种 Janus 激酶（可能是 JAK1）以及 STAT3。促炎细胞因子干扰素-γ 可能部分通过非经典 JAK/STAT 受体信号通路调节上皮水通道蛋白-1 水通道，从而导致与肠道炎症相关的腹泻。
Inflammatory bowel diseases are associated with dysregulated electrolyte and water transport and resultant diarrhea. Aquaporins are transmembrane proteins that function as water channels in intestinal epithelial cells. We investigated the effect of the inflammatory cytokine, interferon-γ, which is a major player in inflammatory bowel diseases, on aquaporin-1 expression in a mouse colonic epithelial cell line, CMT93. CMT93 monolayers were exposed to 10 ng/mL interferon-γ and aquaporin-1 mRNA and protein expressions were measured by real-time PCR and western blot, respectively. In other experiments, CMT93 cells were pretreated with inhibitors or were transfected with siRNA to block the effects of Janus kinases, STATs 1 and 3, or interferon regulatory factor 2, prior to treatment with interferon-γ. Interferon-γ decreased aquaporin-1 expression in mouse intestinal epithelial cells in a manner that did not depend on the classical STAT1/JAK2/IRF-1 pathway, but rather, on an alternate Janus kinase (likely JAK1) as well as on STAT3. The pro-inflammatory cytokine, interferon-γ may contribute to diarrhea associated with intestinal inflammation in part through regulation of the epithelial aquaporin-1 water channel via a non-classical JAK/STAT receptor signalling pathway.
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DOI：
10.1084/jem.191.12.2131
发表时间：
2000-06-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Blanco JC;Contursi C;Salkowski CA;DeWitt DL;Ozato K;Vogel SN
通讯作者：
Vogel SN
DOI：
10.4049/jimmunol.1001442
发表时间：
2011-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Glover LE;Irizarry K;Scully M;Campbell EL;Bowers BE;Aherne CM;Kominsky DJ;MacManus CF;Colgan SP
通讯作者：
Colgan SP
影响因子：
3.7
作者：
Sakai H;Sagara A;Matsumoto K;Hasegawa S;Sato K;Nishizaki M;Shoji T;Horie S;Nakagawa T;Tokuyama S;Narita M
通讯作者：
Narita M
影响因子：
11.5
作者：
Duan, Zhenfeng;Bradner, James E.;Seiden, Michael V.
通讯作者：
Seiden, Michael V.
影响因子：
24.5
作者：
Thiagarajah, Jay R.;Zhao, Dan;Verkman, A. S.
通讯作者：
Verkman, A. S.