ACE2 contributes to the maintenance of mouse epithelial barrier function.
ACE2 contributes to the maintenance of mouse epithelial barrier function.
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ACE2 有助于维持小鼠上皮屏障功能。
DOI：
10.1016/j.bbrc.2020.10.002
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发表时间：
2020-12-17
影响因子：
3.1
通讯作者：
Yan J
中科院分区：
文献类型：
--
作者：
Yu W;Ou X;Liu X;Zhang S;Gao X;Cheng H;Zhu B;Yan J
全世界都受到了新型冠状病毒病（COVID-19）的严重打击。鉴于血管紧张素I转化酶2（ACE 2）是病毒进入分子，了解ACE 2已成为当前COVID-19研究的主要焦点。ACE 2在肠道中高度表达，但其作用尚未完全了解，因此旨在下调ACE 2水平的COVID-19治疗可能会导致不良副作用。因此，深入了解ACE 2在肠道内稳态中的功能值得更仔细的研究，并有助于找到COVID-19的潜在治疗替代方案。方法：利用Ace 2基因敲除小鼠和分离肠类器官的方法，研究ACE 2在肠干性中的作用。用4%葡聚糖硫酸钠建立炎症性肠病（IBD）小鼠模型。定量LGR 5和KI 67水平以反映肠干细胞（ISC）的优点。采用FITC-葡聚糖4（FD-4）试验评价肠屏障功能。结果：Western blotting检测到ACE 2在结肠组织中的表达，与免疫荧光和RT-PCR检测结果一致。此外，Ace 2 −/−类器官显示LRG 5和KI 67水平降低，钙浓度升高。此外，与ace 2 +/+类器官相比，ace 2 −/−类器官的渗透性显著增加。总的来说，ace 2 −/−小鼠比ace 2 +/+小鼠更容易患IBD，包括更早的血便，破坏肠道结构和更明显的体重减轻。结论：我们的数据表明，ACE 2有助于肠干细胞的增殖，因此协调粘膜稳态。
The whole world was hit hard by the coronavirus disease-19 (COVID-19). Given that angiotensin I converting enzyme 2 (ACE2) is the viral entry molecule, understanding ACE2 has become a major focus of current COVID-19 research. ACE2 is highly expressed in the gut, but its role has not been fully understood and thus COVID-19 treatments intending to downregulate ACE2 level may cause untoward side effects. Gaining insight into the functions of ACE2 in gut homeostasis therefore merits closer examination, and is beneficial to find potential therapeutic alternatives for COVID-19. Methods: We took advantage of Ace2 knockout out mice and isolated intestinal organoids to examine the role of ACE2 in intestinal stemness. Inflammatory bowel disease (IBD) mouse model was established by 4% dextran sodium sulfate. LGR5 and KI67 levels were quantitated to reflect the virtue of intestinal stem cells (ISCs). FITC-dextran 4 (FD-4) assay was used to assess intestinal barrier function. Results: Western blotting identified the expression of ACE2 in colon, which was consistent with the results of immunofluorescence and RT-PCR. Moreover, Ace2−/− organoids showed decreased LRG5 and KI67 levels, and elevated calcium concentration. Furthermore, the permeability of ace2−/− organoids was markedly increased compared with ace2+/+ organoids. Collectively, ace2−/− mice were more susceptible than ace2+/+ mice to IBD, including earlier bloody stool, undermined intestinal architecture and more pronounced weight loss. Conclusions: Our data reveal that ACE2 contributes to the proliferation of intestinal stem cells and hence orchestrates the mucosal homeostasis.
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影响因子：
158.5
作者：
Li, Qun;Guan, Xuhua;Feng, Zijian
通讯作者：
Feng, Zijian
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：
11.1
作者：
Shimoda M;Horiuchi K;Sasaki A;Tsukamoto T;Okabayashi K;Hasegawa H;Kitagawa Y;Okada Y
通讯作者：
Okada Y
影响因子：
56.9
作者：
Lamers, Mart M.;Beumer, Joep;Clevers, Hans
通讯作者：
Clevers, Hans
影响因子：
4.6
作者：
Wang, Wang;Bodiga, Sreedhar;Oudit, Gavin Y.
通讯作者：
Oudit, Gavin Y.