Super resolution microscopy analysis reveals increased Orai1 activity in asthma and cystic fibrosis lungs.
Asthma
Cystic fibrosis
Inflammation
Orai1/STIM1
RNAscope
Super resolution microscopy
Journal
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
ISSN: 1873-5010
Titre abrégé: J Cyst Fibros
Pays: Netherlands
ID NLM: 101128966
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
received:
09
03
2022
revised:
01
07
2022
accepted:
04
07
2022
pmc-release:
01
01
2024
pubmed:
13
8
2022
medline:
15
3
2023
entrez:
12
8
2022
Statut:
ppublish
Résumé
In diseases such as asthma and cystic fibrosis (CF), the immune response is dysregulated and the lung is chronically inflamed. Orai1 activation is required for the initiation and persistence of inflammation. However, Orai1 expression in the lung is poorly understood. We therefore tested the hypothesis that Orai1 expression was upregulated in asthmatic and CF lungs. We used LungMAP to analyze single-cell RNAseq data of Orai1 and stromal interaction molecule 1 (STIM1) expression in normal human lungs. We then performed RNAscope analysis and immunostaining on lung sections from normal, asthma, and CF donors. We imaged sections by confocal and super resolution microscopy, and analyzed Orai1 and STIM1 expression in different pulmonary cell types. Orai1 was broadly-expressed, but expression was greatest in immune cells. At mRNA and protein levels, there were no consistent trends in expression levels between the three phenotypes. Orai1 must interact with STIM1 in order to activate and conduct Ca We found evidence that Orai1 was more active in asthma and CF than normal lungs. These data suggest that Orai1 is a relevant target for reducing pulmonary inflammation.
Identifiants
pubmed: 35961837
pii: S1569-1993(22)00602-6
doi: 10.1016/j.jcf.2022.07.003
pmc: PMC9982747
mid: NIHMS1877729
pii:
doi:
Substances chimiques
Calcium Channels
0
Calcium
SY7Q814VUP
ORAI1 Protein
0
ORAI1 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
161-171Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK065988
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL122638
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL122642
Pays : United States
Informations de copyright
Copyright © 2022. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Conflict of Interest Disclosure RT is a founder of Eldec Pharmaceuticals, has equity in this company and serves as its President and Chief Scientific Officer. RT is also listed as an inventor on intellectual property related to Orai1 inhibition. The other authors have nothing to disclose.
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