Background

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.

中文翻译：

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ACE2有助于维持小鼠上皮屏障功能

背景

冠状病毒19号（COVID-19）严重打击了整个世界。鉴于血管紧张素I转换酶2（ACE2）是病毒进入分子，因此了解ACE2已成为当前COVID-19研究的主要重点。ACE2在肠道中高度表达，但其作用尚未完全了解，因此打算下调ACE2水平的COVID-19治疗可能会导致不良的副作用。因此，深入了解ACE2在肠道稳态中的功能值得仔细检查，并且有利于找到COVID-19的潜在治疗替代方案。方法：我们利用了Ace2剔除小鼠和分离的肠道类器官，检查ACE2在肠道干中的作用。用4％葡聚糖硫酸钠建立炎症性肠病（IBD）小鼠模型。定量LGR5和KI67水平以反映肠道干细胞（ISC）的优点。使用FITC-葡聚糖4（FD-4）分析评估肠屏障功能。结果：Western blotting鉴定了ACE2在结肠中的表达，这与免疫荧光和RT-PCR的结果一致。此外，Ace2 ^-/-类器官动物显示出LRG5和KI67含量降低，钙浓度升高。此外，与ace2 ^{+ / +}相比，ace2 ^--/-类器官的渗透性显着提高类器官。总体而言，ace2 ^-/-小鼠比ace2 ^{+ / +}小鼠更易受IBD感染，包括较早的血便，破坏肠道结构和更明显的体重减轻。结论：我们的数据表明ACE2促进肠道干细胞的增殖，从而协调了粘膜稳态。