Ace2 and Tmprss2 Expressions Are Regulated by Dhx32 and Influence the Gastrointestinal Symptoms Caused by SARS-CoV-2.
Ace2 and Tmprss2 Expressions Are Regulated by Dhx32 and Influence the Gastrointestinal Symptoms Caused by SARS-CoV-2.
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DOI：
10.3390/jpm11111212
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发表时间：
2021-11-16
影响因子：
--
通讯作者：
Lu L
中科院分区：
文献类型：
--
作者：
Xu F;Gao J;Orgil BO;Bajpai AK;Gu Q;Purevjav E;Davenport AS;Li K;Towbin JA;Black DD;Pierre JF;Lu L
研究表明，胃肠道是感染SARS-CoV-2和2019冠状病毒病（COVID-19）的最重要途径之一。由于SARS-CoV-2的细胞进入依赖于刺突蛋白的ACE2受体和TMPRSS2启动，因此了解这两种蛋白及其同源转录物相互作用并影响COVID-19发病机制的分子机制非常重要。在这项研究中，我们使用系统遗传学方法和高度多样化的BXD小鼠品系的扩展家族，量化了胃肠道组织中Tmprss2和Ace2 mRNA的表达、关联、遗传调节剂和分子途径。结果表明，Tmprss2和Ace2在胃肠道组织中均高表达，且共变显著。我们在7号染色体上发现了一个控制Tmprss2和Ace2表达的显著数量性状位点。Dhx32是这个区间内最强的候选基因。共表达网络分析表明，Tmprss2和Ace2都位于与其他gi相关性状显著相关的同一模块。蛋白质-蛋白质相互作用分析表明，该模块中的枢纽基因与昼夜节律有关。总的来说，我们的数据表明，具有昼夜节律表达的基因可能对COVID-19疾病有影响，并与COVID-19的时间和治疗有关。
Studies showed that the gastrointestinal (GI) tract is one of the most important pathways for SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19). As SARS-CoV-2 cellular entry depends on the ACE2 receptor and TMPRSS2 priming of the spike protein, it is important to understand the molecular mechanisms through which these two proteins and their cognate transcripts interact and influence the pathogenesis of COVID-19. In this study, we quantified the expression, associations, genetic modulators, and molecular pathways for Tmprss2 and Ace2 mRNA expressions in GI tissues using a systems genetics approach and the expanded family of highly diverse BXD mouse strains. The results showed that both Tmprss2 and Ace2 are highly expressed in GI tissues with significant covariation. We identified a significant expression quantitative trait locus on chromosome 7 that controls the expression of both Tmprss2 and Ace2. Dhx32 was found to be the strongest candidate in this interval. Co-expression network analysis demonstrated that both Tmprss2 and Ace2 were located at the same module that is significantly associated with other GI-related traits. Protein–protein interaction analysis indicated that hub genes in this module are linked to circadian rhythms. Collectively, our data suggested that genes with circadian rhythms of expression may have an impact on COVID-19 disease, with implications related to the timing and treatment of COVID-19.
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影响因子：
5.4
作者：
Heurich, Adeline;Hofmann-Winkler, Heike;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan
影响因子：
3.8
作者：
HALEY, CS;KNOTT, SA
通讯作者：
KNOTT, SA
ACE2将氨基酸营养不良与微生物生态学和肠炎联系起来。
影响因子：
64.8
作者：
Hashimoto T;Perlot T;Rehman A;Trichereau J;Ishiguro H;Paolino M;Sigl V;Hanada T;Hanada R;Lipinski S;Wild B;Camargo SM;Singer D;Richter A;Kuba K;Fukamizu A;Schreiber S;Clevers H;Verrey F;Rosenstiel P;Penninger JM
通讯作者：
Penninger JM
影响因子：
28.3
作者：
Gorbalenya, Alexander E.;Baker, Susan C.;Ziebuhr, John
通讯作者：
Ziebuhr, John
影响因子：
5.4
作者：
Glowacka, Ilona;Bertram, Stephanie;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan