MicroRNA-98 and let-7 regulate expression of suppressor of cytokine signaling 4 in biliary epithelial cells in response to Cryptosporidium parvum infection.

MicroRNA-98 and let-7 regulate expression of suppressor of cytokine signaling 4 in biliary epithelial cells in response to Cryptosporidium parvum infection.
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DOI:
10.1086/653212
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发表时间:
2010-07-01
期刊:
The Journal of infectious diseases
影响因子:
--
通讯作者:
Chen XM
Chen XM
中科院分区:
其他
文献类型:
--
作者:
Hu G;Zhou R;Liu J;Gong AY;Chen XM

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细胞因子诱导的Src同源2蛋白(CIS)和细胞因子信号蛋白抑制因子(SOCS)的表达是宿主细胞对病原体感染反应的重要组成部分。我们之前证明,小隐孢子虫感染下调miR-98和let-7诱导胆道上皮细胞中CIS的表达。我们在这里报道了miR-98和let-7的下调也协调了小孢子虫感染后SOCS4的上皮表达。miR-98或let-7靶向SOCS4 3'-非翻译区导致翻译抑制。miR-98的功能操作导致SOCS4蛋白表达的相互改变。转染miR-98前体可消除小虫卵刺激的SOCS4上调。此外,SOCS4在上皮细胞中的表达对小弧菌诱导的信号转导和转录蛋白激活因子的磷酸化有抑制作用。这些数据表明,mirna在协调调节上皮细胞中CIS/SOCS表达以应对小孢子虫感染中发挥重要作用。
Expression of the cytokine-inducible Src homology 2 protein (CIS) and suppressors of cytokine signaling proteins (SOCS) represents an important element of host cell reactions in response to pathogen infection. We previously demonstrated that Cryptosporidium parvum infection downregulates miR-98 and let-7 to induce CIS expression in biliary epithelial cells. We reported here that downregulation of miR-98 and let-7 also coordinates epithelial expression of SOCS4 following C. parvum infection. Targeting of SOCS4 3'-untranslated region by miR-98 or let-7 resulted in translational repression. Functional manipulation of miR-98 caused reciprocal alterations in SOCS4 protein expression. Transfection of miR-98 precursor abolished C. parvum-stimulated SOCS4 upregulation. Moreover, expression of SOCS4 in epithelial cells showed an inhibitory effect on phosphorylation of signal transducers and activators of transcription proteins induced by C. parvum. These data suggest an important role for miRNAs in the coordinated regulation of CIS/SOCS expression in epithelial cells in response to C. parvum infection.
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