ArticleJournal of cystic fibrosis : official journal of the European Cystic Fibrosis Society2021
The proteostatic network chaperome is downregulated in F508del homozygote cystic fibrosis.
Article in Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 7 citations in OpenAlex.
- Recent developments in cystic fibrosis drug discovery: where are we today?Expert opinion on drug discovery · 2025Review
- APPLICATION OF QUANTILE DISCRETIZATION AND BAYESIAN NETWORK ANALYSIS TO PUBLICLY AVAILABLE CYSTIC FIBROSIS DATA SETS.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2024Article
- Expression ofAmerican journal of respiratory cell and molecular biology · 2022Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCF patients demonstrate clinical heterogeneity and much remains unknown about how to risk stratify individuals for disease progression. The most common cystic fibrosis mutation, F508del, is a protein folding mutation that has been shown in vitro to negatively affect proteostasis and CFTR transcription. Since CFTR is expressed in the nasal epithelium, we hypothesized that by using unbiased transcriptomics we could gain clinically relevant insights about differential gene expression and heterogeneity in CF patients as well as assess proteostatic dysfunction in the nasal epithelium.
methodsUsing nasal curettage and RNA-seq we assessed differential gene expression in F508del homozygotes compared to healthy volunteers. Gene set enrichment analysis was performed using a list of known chaperones. Pilot and validation cohorts were studied.
resultsPCA analysis and gene expression heatmaps exhibited greater heterogeneity among CF than healthy volunteers. Differentially expressed genes were enriched for the downregulation of ciliary/microtubular genes and the upregulation of inflammatory/immune response genes in F508del homozygotes compared to healthy volunteers. Gene set analysis identified negative enrichment for chaperone genes and decreased CFTR transcription in the F508del homozygotes. We also found preliminary evidence for the recently identified ionocyte in the nasal specimens.
conclusionCF patients homozygous for F508del demonstrate heterogeneous gene expression profiles, proteostatic dysregulation, and reduced CFTR transcription. Larger studies are needed to determine whether nasal epithelial gene transcription profiles can be leveraged for insights into disease heterogeneity.
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