tetano
Editor, Senior Moderator
Biochem Biophys Res Commun
. 2020 Oct 20;S0006-291X(20)31906-9.
doi: 10.1016/j.bbrc.2020.10.002. Online ahead of print.
ACE2 contributes to the maintenance of mouse epithelial barrier function
Wei Yu[SUP] 1 [/SUP], Xianhong Ou[SUP] 2 [/SUP], Xiaofan Liu[SUP] 1 [/SUP], Shuaixu Zhang[SUP] 1 [/SUP], Xinxin Gao[SUP] 1 [/SUP], Hongju Cheng[SUP] 1 [/SUP], Baoliang Zhu[SUP] 1 [/SUP], Jing Yan[SUP] 3 [/SUP]
Affiliations
Abstract
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[SUP]-/-[/SUP] organoids showed decreased LRG5 and KI67 levels, and elevated calcium concentration. Furthermore, the permeability of ace2[SUP]-/-[/SUP] organoids was markedly increased compared with ace2[SUP]+/+[/SUP] organoids. Collectively, ace2[SUP]-/-[/SUP] mice were more susceptible than ace2[SUP]+/+[/SUP] 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.
Keywords: ACE2; Inflammatory bowel disease; Mucosal homeostasis; Organoids.
. 2020 Oct 20;S0006-291X(20)31906-9.
doi: 10.1016/j.bbrc.2020.10.002. Online ahead of print.
ACE2 contributes to the maintenance of mouse epithelial barrier function
Wei Yu[SUP] 1 [/SUP], Xianhong Ou[SUP] 2 [/SUP], Xiaofan Liu[SUP] 1 [/SUP], Shuaixu Zhang[SUP] 1 [/SUP], Xinxin Gao[SUP] 1 [/SUP], Hongju Cheng[SUP] 1 [/SUP], Baoliang Zhu[SUP] 1 [/SUP], Jing Yan[SUP] 3 [/SUP]
Affiliations
- PMID: 33097186
- DOI: 10.1016/j.bbrc.2020.10.002
Abstract
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[SUP]-/-[/SUP] organoids showed decreased LRG5 and KI67 levels, and elevated calcium concentration. Furthermore, the permeability of ace2[SUP]-/-[/SUP] organoids was markedly increased compared with ace2[SUP]+/+[/SUP] organoids. Collectively, ace2[SUP]-/-[/SUP] mice were more susceptible than ace2[SUP]+/+[/SUP] 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.
Keywords: ACE2; Inflammatory bowel disease; Mucosal homeostasis; Organoids.