SARS-CoV-2 Receptor Angiotensin I-Converting Enzyme Type 2 (ACE2) Is Expressed in Human Pancreatic β-Cells and in the Human Pancreas Microvasculature.
SARS-CoV-2 Receptor Angiotensin I-Converting Enzyme Type 2 (ACE2) Is Expressed in Human Pancreatic β-Cells and in the Human Pancreas Microvasculature.
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DOI：
10.3389/fendo.2020.596898
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发表时间：
2020
影响因子：
5.2
通讯作者：
Dotta F
中科院分区：
文献类型：
--
作者：
Fignani D;Licata G;Brusco N;Nigi L;Grieco GE;Marselli L;Overbergh L;Gysemans C;Colli ML;Marchetti P;Mathieu C;Eizirik DL;Sebastiani G;Dotta F
越来越多的证据表明，血管紧张素转换酶2（ACE 2）的表达是SARS-CoV-2感染许可的必要步骤。鉴于最近的数据突出了COVID-19和糖尿病之间的关联，仍然缺乏旨在评估人类胰腺中ACE 2表达模式分布的详细分析。在这里，我们利用INNODIA网络EUnPOD生物样本库收集，在mRNA和蛋白质水平上，在多个人胰腺组织中使用多种方法彻底分析ACE 2。使用多种试剂和抗体，我们表明ACE 2在人胰岛中表达，其中它优先在产生胰岛素的β细胞亚群中表达。ACE 2也在胰腺微血管周细胞中高度表达，在罕见的分散导管细胞中中度表达。通过使用不同的ACE 2抗体，我们表明最近描述的短ACE 2同种型也在人β细胞中预先表达。最后，使用RT-qPCR、RNA-seq和高含量成像筛选分析，我们证明促炎细胞因子（而不是棕榈酸）增加β细胞系EndoC-βH1和原代人胰岛中ACE 2的表达。综上所述，我们的数据表明SARS-CoV-2和糖尿病之间通过胰腺微血管和/或导管细胞的假定感染和/或通过直接β细胞病毒嗜性的潜在联系。
Increasing evidence demonstrated that the expression of Angiotensin I-Converting Enzyme type 2 (ACE2) is a necessary step for SARS-CoV-2 infection permissiveness. In light of the recent data highlighting an association between COVID-19 and diabetes, a detailed analysis aimed at evaluating ACE2 expression pattern distribution in human pancreas is still lacking. Here, we took advantage of INNODIA network EUnPOD biobank collection to thoroughly analyze ACE2, both at mRNA and protein level, in multiple human pancreatic tissues and using several methodologies. Using multiple reagents and antibodies, we showed that ACE2 is expressed in human pancreatic islets, where it is preferentially expressed in subsets of insulin producing β-cells. ACE2 is also highly expressed in pancreas microvasculature pericytes and moderately expressed in rare scattered ductal cells. By using different ACE2 antibodies we showed that a recently described short-ACE2 isoform is also prevalently expressed in human β-cells. Finally, using RT-qPCR, RNA-seq and High-Content imaging screening analysis, we demonstrated that pro-inflammatory cytokines, but not palmitate, increase ACE2 expression in the β-cell line EndoC-βH1 and in primary human pancreatic islets. Taken together, our data indicate a potential link between SARS-CoV-2 and diabetes through putative infection of pancreatic microvasculature and/or ductal cells and/or through direct β-cell virus tropism.
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影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P
影响因子：
24.3
作者：
Guan, Wei-jie;Liang, Wen-hua;He, Jian-xing
通讯作者：
He, Jian-xing
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
7.3
作者：
Hamming, I;Timens, W;van Goor, H
通讯作者：
van Goor, H
影响因子：
9.9
作者：
Hikmet, Feria;Mear, Loren;Lindskog, Cecilia
通讯作者：
Lindskog, Cecilia