{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bampi GB"],"funding":["NIDDK NIH HHS","Burroughs Wellcome Fund","Cystic Fibrosis Foundation","NHLBI NIH HHS","Cystic Fibrosis Trust"],"pagination":["1021-1026"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7932027"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["19(6)"],"pubmed_abstract":["<h4>Background</h4>Chronic inflammation is a hallmark among patients with cystic fibrosis (CF). We explored whether mutation-induced (F508del) misfolding of the cystic fibrosis transmembrane conductance regulator (CFTR), and/or secondary colonization with opportunistic pathogens, activate tissue remodeling and innate immune response drivers.<h4>Methods</h4>Using RNA-seq to interrogate global gene expression profiles, we analyzed stress response signaling cascades in primary human bronchial epithelia (HBE) and intestinal organoids.<h4>Results</h4>Primary HBE acquired from CF patients with advanced disease and prolonged exposure to pathogenic microorganisms display a clear molecular signature of activated tissue remodeling pathways, unfolded protein response (UPR), and chronic inflammation. Furthermore, CFTR misfolding induces inflammatory signaling cascades in F508del patient-derived organoids from both the distal small intestine and colon.<h4>Conclusion</h4>Despite the small patient cohort size, this proof-of-principle study supports the use of RNA-seq as a means to both identify CF-specific signaling profiles in various tissues and evaluate disease heterogeneity. Our global transcriptomic data is a useful resource for the CF research community for analyzing other gene expression sets influencing CF disease signature but also transcriptionally contributing to CF heterogeneity."],"journal":["Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society"],"pubmed_title":["Global assessment of the integrated stress response in CF patient-derived airway and intestinal tissues."],"pmcid":["PMC7932027"],"funding_grant_id":["R01 DK068196","SRC011","K99 HL151965","R01 HL136414"],"pubmed_authors":["Bampi GB","Bijvelds MJC","Rauscher R","Frizzell RA","de Jonge HR","Sorscher EJ","Oliver KE","Wagner J","Ignatova Z","Kirchner S","Santos LA"],"additional_accession":[]},"is_claimable":false,"name":"Global assessment of the integrated stress response in CF patient-derived airway and intestinal tissues.","description":"<h4>Background</h4>Chronic inflammation is a hallmark among patients with cystic fibrosis (CF). We explored whether mutation-induced (F508del) misfolding of the cystic fibrosis transmembrane conductance regulator (CFTR), and/or secondary colonization with opportunistic pathogens, activate tissue remodeling and innate immune response drivers.<h4>Methods</h4>Using RNA-seq to interrogate global gene expression profiles, we analyzed stress response signaling cascades in primary human bronchial epithelia (HBE) and intestinal organoids.<h4>Results</h4>Primary HBE acquired from CF patients with advanced disease and prolonged exposure to pathogenic microorganisms display a clear molecular signature of activated tissue remodeling pathways, unfolded protein response (UPR), and chronic inflammation. Furthermore, CFTR misfolding induces inflammatory signaling cascades in F508del patient-derived organoids from both the distal small intestine and colon.<h4>Conclusion</h4>Despite the small patient cohort size, this proof-of-principle study supports the use of RNA-seq as a means to both identify CF-specific signaling profiles in various tissues and evaluate disease heterogeneity. Our global transcriptomic data is a useful resource for the CF research community for analyzing other gene expression sets influencing CF disease signature but also transcriptionally contributing to CF heterogeneity.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Nov","modification":"2024-11-21T00:57:57.792Z","creation":"2021-03-07T08:15:50Z"},"accession":"S-EPMC7932027","cross_references":{"pubmed":["32451204"],"doi":["10.1016/j.jcf.2020.04.005"]}}