Super resolution microscopy analysis reveals increased Orai1 activity in asthma and cystic fibrosis lungs

Autor: Alexandra S. Goriounova, Rodney C. Gilmore, Joe A. Wrennall, Robert Tarran
Rok vydání: 2023
Předmět:
Zdroj: Journal of Cystic Fibrosis. 22:161-171
ISSN: 1569-1993
DOI: 10.1016/j.jcf.2022.07.003
Popis: 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 CaWe 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.
Databáze: OpenAIRE