tetano
Editor, Senior Moderator
J Pharmacol Sci
. 2022 Jul;149(3):139-146.
doi: 10.1016/j.jphs.2022.04.010. Epub 2022 May 2.
SARS-CoV-2 induces barrier damage and inflammatory responses in the human iPSC-derived intestinal epithelium
Shigeru Yamada[SUP] 1 [/SUP], Takamasa Noda[SUP] 2 [/SUP], Kaori Okabe[SUP] 3 [/SUP], Shota Yanagida[SUP] 1 [/SUP], Motohiro Nishida[SUP] 4 [/SUP], Yasunari Kanda[SUP] 5 [/SUP]
Affiliations
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread and led to global health crises. COVID-19 causes well-known respiratory failure and gastrointestinal symptoms, such as diarrhea, nausea, and vomiting. Thus, human gastrointestinal cell models are urgently needed for COVID-19 research; however, it is difficult to obtain primary human intestinal cells. In this study, we examined whether human induced pluripotent stem cell (iPSC)-derived small intestinal epithelial cells (iPSC-SIECs) could be used as a SARS-CoV-2 infection model. We observed that iPSC-SIECs, such as absorptive and Paneth cells, were infected with SARS-CoV-2, and remdesivir treatment decreased intracellular SARS-CoV-2 replication in iPSC-SIECs. SARS-CoV-2 infection decreased expression levels of tight junction markers, ZO-3 and CLDN1, and transepithelial electrical resistance (TEER), which evaluates the integrity of tight junction dynamics. In addition, SARS-CoV-2 infection increased expression levels of proinflammatory genes, which are elevated in patients with COVID-19. These findings suggest iPSC-SIECs as a useful in vitro model for elucidating COVID-19 pathology and drug development.
Keywords: Barrier functions; COVID-19; SARS-CoV-2; Small intestinal epithelial cells; iPSC.
. 2022 Jul;149(3):139-146.
doi: 10.1016/j.jphs.2022.04.010. Epub 2022 May 2.
SARS-CoV-2 induces barrier damage and inflammatory responses in the human iPSC-derived intestinal epithelium
Shigeru Yamada[SUP] 1 [/SUP], Takamasa Noda[SUP] 2 [/SUP], Kaori Okabe[SUP] 3 [/SUP], Shota Yanagida[SUP] 1 [/SUP], Motohiro Nishida[SUP] 4 [/SUP], Yasunari Kanda[SUP] 5 [/SUP]
Affiliations
- PMID: 35641026
- DOI: 10.1016/j.jphs.2022.04.010
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread and led to global health crises. COVID-19 causes well-known respiratory failure and gastrointestinal symptoms, such as diarrhea, nausea, and vomiting. Thus, human gastrointestinal cell models are urgently needed for COVID-19 research; however, it is difficult to obtain primary human intestinal cells. In this study, we examined whether human induced pluripotent stem cell (iPSC)-derived small intestinal epithelial cells (iPSC-SIECs) could be used as a SARS-CoV-2 infection model. We observed that iPSC-SIECs, such as absorptive and Paneth cells, were infected with SARS-CoV-2, and remdesivir treatment decreased intracellular SARS-CoV-2 replication in iPSC-SIECs. SARS-CoV-2 infection decreased expression levels of tight junction markers, ZO-3 and CLDN1, and transepithelial electrical resistance (TEER), which evaluates the integrity of tight junction dynamics. In addition, SARS-CoV-2 infection increased expression levels of proinflammatory genes, which are elevated in patients with COVID-19. These findings suggest iPSC-SIECs as a useful in vitro model for elucidating COVID-19 pathology and drug development.
Keywords: Barrier functions; COVID-19; SARS-CoV-2; Small intestinal epithelial cells; iPSC.