Expression of SARS‐CoV‐2 entry factors, electrolyte, and mineral transporters in different mouse intestinal epithelial cell types

Abstract Angiotensin‐converting enzyme 2 (ACE2) and transmembrane proteases (TMPRSS) are multifunctional proteins required for SARS‐CoV‐2 infection or for amino acid (AA) transport, and are abundantly expressed in mammalian small intestine, but the identity of the intestinal cell type(s) and sites o...

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Autores principales:	Sarah C. Pearce, Panan Suntornsaratoon, Kunihiro Kishida, Arwa Al‐Jawadi, Joshua Guardia, Ian Nadler, Juan Flores, Reilly Shiarella, Madelyn Auvinen, Shiyan Yu, Nan Gao, Ronaldo P. Ferraris
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	ACE2 calcium iron mucosa TMPRSS villus Physiology QP1-981
Acceso en línea:	https://doaj.org/article/414222a2d97b4d8f84492c607555991b
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spelling	oai:doaj.org-article:414222a2d97b4d8f84492c607555991b2021-11-15T09:54:40ZExpression of SARS‐CoV‐2 entry factors, electrolyte, and mineral transporters in different mouse intestinal epithelial cell types2051-817X10.14814/phy2.15061https://doaj.org/article/414222a2d97b4d8f84492c607555991b2021-11-01T00:00:00Zhttps://doi.org/10.14814/phy2.15061https://doaj.org/toc/2051-817XAbstract Angiotensin‐converting enzyme 2 (ACE2) and transmembrane proteases (TMPRSS) are multifunctional proteins required for SARS‐CoV‐2 infection or for amino acid (AA) transport, and are abundantly expressed in mammalian small intestine, but the identity of the intestinal cell type(s) and sites of expression are unclear. Here we determined expression of SARS‐CoV‐2 entry factors in different cell types and then compared it to that of representative AA, electrolyte, and mineral transporters. We tested the hypothesis that SARS‐CoV‐2, AA, electrolyte, and mineral transporters are expressed heterogeneously in different intestinal cell types by making mouse enteroids enriched in enterocytes (ENT), goblet (GOB), Paneth (PAN), or stem (ISC) cells. Interestingly, the expression of ACE2 was apical and modestly greater in ENT, the same pattern observed for its associated AA transporters B0AT1 and SIT1. TMPRSS2 and TMPRSS4 were more highly expressed in crypt‐residing ISC. Expression of electrolyte transporters was dramatically heterogeneous. DRA, NBCe1, and NHE3 were greatest in ENT, while those of CFTR and NKCC1 that play important roles in secretory diarrhea, were mainly expressed in ISC and PAN that also displayed immunohistochemically abundant basolateral NKCC1. Intestinal iron transporters were generally expressed higher in ENT and GOB, while calcium transporters were expressed mainly in PAN. Heterogeneous expression of its entry factors suggests that the ability of SARS‐CoV‐2 to infect the intestine may vary with cell type. Parallel cell‐type expression patterns of ACE2 with B0AT1 and SIT1 provides further evidence of ACE2's multifunctional properties and importance in AA absorption.Sarah C. PearcePanan SuntornsaratoonKunihiro KishidaArwa Al‐JawadiJoshua GuardiaIan NadlerJuan FloresReilly ShiarellaMadelyn AuvinenShiyan YuNan GaoRonaldo P. FerrarisWileyarticleACE2calciumironmucosaTMPRSSvillusPhysiologyQP1-981ENPhysiological Reports, Vol 9, Iss 21, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ACE2 calcium iron mucosa TMPRSS villus Physiology QP1-981
spellingShingle	ACE2 calcium iron mucosa TMPRSS villus Physiology QP1-981 Sarah C. Pearce Panan Suntornsaratoon Kunihiro Kishida Arwa Al‐Jawadi Joshua Guardia Ian Nadler Juan Flores Reilly Shiarella Madelyn Auvinen Shiyan Yu Nan Gao Ronaldo P. Ferraris Expression of SARS‐CoV‐2 entry factors, electrolyte, and mineral transporters in different mouse intestinal epithelial cell types
description	Abstract Angiotensin‐converting enzyme 2 (ACE2) and transmembrane proteases (TMPRSS) are multifunctional proteins required for SARS‐CoV‐2 infection or for amino acid (AA) transport, and are abundantly expressed in mammalian small intestine, but the identity of the intestinal cell type(s) and sites of expression are unclear. Here we determined expression of SARS‐CoV‐2 entry factors in different cell types and then compared it to that of representative AA, electrolyte, and mineral transporters. We tested the hypothesis that SARS‐CoV‐2, AA, electrolyte, and mineral transporters are expressed heterogeneously in different intestinal cell types by making mouse enteroids enriched in enterocytes (ENT), goblet (GOB), Paneth (PAN), or stem (ISC) cells. Interestingly, the expression of ACE2 was apical and modestly greater in ENT, the same pattern observed for its associated AA transporters B0AT1 and SIT1. TMPRSS2 and TMPRSS4 were more highly expressed in crypt‐residing ISC. Expression of electrolyte transporters was dramatically heterogeneous. DRA, NBCe1, and NHE3 were greatest in ENT, while those of CFTR and NKCC1 that play important roles in secretory diarrhea, were mainly expressed in ISC and PAN that also displayed immunohistochemically abundant basolateral NKCC1. Intestinal iron transporters were generally expressed higher in ENT and GOB, while calcium transporters were expressed mainly in PAN. Heterogeneous expression of its entry factors suggests that the ability of SARS‐CoV‐2 to infect the intestine may vary with cell type. Parallel cell‐type expression patterns of ACE2 with B0AT1 and SIT1 provides further evidence of ACE2's multifunctional properties and importance in AA absorption.
format	article
author	Sarah C. Pearce Panan Suntornsaratoon Kunihiro Kishida Arwa Al‐Jawadi Joshua Guardia Ian Nadler Juan Flores Reilly Shiarella Madelyn Auvinen Shiyan Yu Nan Gao Ronaldo P. Ferraris
author_facet	Sarah C. Pearce Panan Suntornsaratoon Kunihiro Kishida Arwa Al‐Jawadi Joshua Guardia Ian Nadler Juan Flores Reilly Shiarella Madelyn Auvinen Shiyan Yu Nan Gao Ronaldo P. Ferraris
author_sort	Sarah C. Pearce
title	Expression of SARS‐CoV‐2 entry factors, electrolyte, and mineral transporters in different mouse intestinal epithelial cell types
title_short	Expression of SARS‐CoV‐2 entry factors, electrolyte, and mineral transporters in different mouse intestinal epithelial cell types
title_full	Expression of SARS‐CoV‐2 entry factors, electrolyte, and mineral transporters in different mouse intestinal epithelial cell types
title_fullStr	Expression of SARS‐CoV‐2 entry factors, electrolyte, and mineral transporters in different mouse intestinal epithelial cell types
title_full_unstemmed	Expression of SARS‐CoV‐2 entry factors, electrolyte, and mineral transporters in different mouse intestinal epithelial cell types
title_sort	expression of sars‐cov‐2 entry factors, electrolyte, and mineral transporters in different mouse intestinal epithelial cell types
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/414222a2d97b4d8f84492c607555991b
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Expression of SARS‐CoV‐2 entry factors, electrolyte, and mineral transporters in different mouse intestinal epithelial cell types

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