Interferon-γ induces AT2 receptor expression in fibroblasts by Jak/STAT pathway and interferon regulatory factor-1
Interferon-γ induces AT2 receptor expression in fibroblasts by Jak/STAT pathway and interferon regulatory factor-1
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DOI：
10.1161/01.res.86.2.233
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发表时间：
2000-02-04
影响因子：
20.1
通讯作者：
Minokoshi, Y
中科院分区：
文献类型：
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作者：
Horiuchi, M;Hayashida, W;Minokoshi, Y
血管紧张素II型2 （AT(2)）受体的表达与细胞生长、分化和/或损伤密切相关。我们检测了干扰素(IFN)- γ对小鼠成纤维细胞R3T3 AT受体表达的影响，并证明IFN- γ处理增加了AT(2)受体mRNA的表达及其结合。干扰素调节因子(IRF)-1在ifn - γ刺激后被诱导到小鼠成纤维细胞R3T3细胞中，电泳迁移量转移实验显示，ifn - γ刺激后，IRF-1与AT受体基因启动子区IRF特异性结合序列的结合增加。IRF-1基因启动子包含一个ifn - γ激活序列（GAS）基序，用于可能结合信号换能器和转录激活子（STAT）。事实上，在R3T3细胞中，ifn - γ处理通过酪氨酸磷酸化导致Janus激酶（Jak） 1、Jak2和STAT1的快速激活。用GAS探针进行的电泳迁移率转移分析显示，在ifn - γ刺激下，STAT1与IRF-1基因启动子的结合增加。转染gas结合寡核苷酸抑制ifn - γ对IRF-1产生的影响，导致AT受体反式激活。综上所述，我们的数据表明，ifn - γ通过激活细胞内Jak/STAT通路和IRF-1的产物离子，上调R3T3细胞中AT受体的表达。
The expression of angiotensin II type 2 (AT(2)) receptor is closely associated with cell growth, differentiation, and/or injury. We examined the effect of interferon (IFN)-gamma on AT, receptor expression in mouse fibroblast R3T3 cells and demonstrated that IFN-gamma treatment increased the expression of AT(2) receptor mRNA as well as its binding. Interferon regulatory factor (IRF)-1 was induced in mouse fibroblast R3T3 cells after IFN-gamma stimulation, and electrophoretic mobility shift assay showed an increase in IRF-1 binding with the IRF-specific binding sequence in the AT, receptor gene promoter region after IFN-gamma stimulation. The IRF-1 gene promoter contains an IFN-gamma-activated sequence (GAS) motif for possible binding of signal transducer(s) and activator(s) of transcription (STAT). Indeed, in R3T3 cells, IFN-gamma treatment resulted in rapid activation of Janus kinase (Jak) 1, Jak2, and STAT1 via tyrosine phosphorylation. Electrophoretic mobility shift assay with the GAS probe revealed increased STAT1 binding to the IRF-1 gene promoter in response to IFN-gamma stimulation. Transfection of GAS-binding oligonucleotides inhibited the effect of IFN-gamma on IRF-1 production, resulting in the AT, receptor trans-activation. Taken together, our data show that IFN-gamma upregulates AT, receptor expression in R3T3 cells via the activation of the intracellular Jak/STAT pathway and product:ion of IRF-1.