Glucocorticoid Receptor Inhibits the Progression of Schistosomiasis Hepatic Fibrosis Through Inducing Circadian Clock Gene Per1.

IF 5 2区 医学 Q2 IMMUNOLOGY
Rui Tang, Tao Sun, Zhou Xing, XiaoBin Fan, PengYue Jiang, Bin Le, KaiWei Jia, YiLi Cai, XiaoJuan Bi, DongMei Zhang, RenYong Lin, Xing He
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引用次数: 0

Abstract

Hepatic fibrosis is the leading cause of morbidity and mortality in schistosomiasis, and transcription factors (TF) may become potential therapeutic targets for this disease. Here, we found that a TF, NR3C1, was significantly downregulated in hepatic stellate cells (HSC), the effector cell of hepatic fibrosis, from mice infected with Schistosoma japonicum using RNA sequencing. Activation of NR3C1 using dexamethasone blocked HSC activation and hepatic fibrosis progression, while these effects were completely abolished upon specific deletion of NR3C1 in HSCs. Genome-wide binding site and transcriptome analyses suggested that Per1, a circadian clock gene, was under the direct control of NR3C1 through binding the glucocorticoid response elements, and it was responsible for the inhibitory effect of NR3C1 on HSC activation. Therefore, NR3C1 is a key TF in the activation of HSCs and a potential therapeutic target for hepatic schistosomiasis.

糖皮质激素受体通过诱导昼夜节律钟基因 Per1 抑制血吸虫病肝纤维化的进展
肝纤维化是血吸虫病发病和死亡的主要原因,转录因子(TF)可能成为血吸虫病的潜在治疗靶点。本研究通过RNA测序发现,日本血吸虫感染小鼠的肝星状细胞(HSC)是肝纤维化的效应细胞,其TF NR3C1显著下调。使用地塞米松激活NR3C1可阻断HSC的激活和肝纤维化进展,而在HSC中特异性删除NR3C1后,这些作用被完全消除。全基因组结合位点和转录组分析表明,生物钟基因Per1通过结合糖皮质激素反应元件受到NR3C1的直接控制,并负责NR3C1对HSC活化的抑制作用。因此,NR3C1是激活hsc的关键TF,也是肝血吸虫病的潜在治疗靶点。
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来源期刊
Journal of Infectious Diseases
Journal of Infectious Diseases 医学-传染病学
CiteScore
13.50
自引率
3.10%
发文量
449
审稿时长
2-4 weeks
期刊介绍: Published continuously since 1904, The Journal of Infectious Diseases (JID) is the premier global journal for original research on infectious diseases. The editors welcome Major Articles and Brief Reports describing research results on microbiology, immunology, epidemiology, and related disciplines, on the pathogenesis, diagnosis, and treatment of infectious diseases; on the microbes that cause them; and on disorders of host immune responses. JID is an official publication of the Infectious Diseases Society of America.
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