Co-Expression Analysis of Airway Epithelial Transcriptome in Asthma Patients with Eosinophilic vs. Non-Eosinophilic Airway Infiltration.
Pawel Kozlik-SiwiecSylwia Buregwa-CzumaIzabela ZawlikSylwia DziedzinaAleksander MyszkaJoanna Zuk-KuwikAndżelika Siwiec-KoźlikJacek ZarychtaKrzysztof OkonLech ZarebaJerzy SojaBogdan JakielaMichał KepskiJan G BazanStanisława Bazan-SochaPublished in: International journal of molecular sciences (2023)
Asthma heterogeneity complicates the search for targeted treatment against airway inflammation and remodeling. We sought to investigate relations between eosinophilic inflammation, a phenotypic feature frequent in severe asthma, bronchial epithelial transcriptome, and functional and structural measures of airway remodeling. We compared epithelial gene expression, spirometry, airway cross-sectional geometry (computed tomography), reticular basement membrane thickness (histology), and blood and bronchoalveolar lavage (BAL) cytokines of n = 40 moderate to severe eosinophilic (EA) and non-eosinophilic asthma (NEA) patients distinguished by BAL eosinophilia. EA patients showed a similar extent of airway remodeling as NEA but had an increased expression of genes involved in the immune response and inflammation (e.g., KIR3DS1 ), reactive oxygen species generation ( GYS2 , ATPIF1 ), cell activation and proliferation ( ANK3 ), cargo transporting ( RAB4B , CPLX2 ), and tissue remodeling ( FBLN1 , SOX14 , GSN ), and a lower expression of genes involved in epithelial integrity (e.g., GJB1 ) and histone acetylation ( SIN3A ). Genes co-expressed in EA were involved in antiviral responses (e.g., ATP1B1 ), cell migration ( EPS8L1 , STOML3 ), cell adhesion ( RAPH1 ), epithelial-mesenchymal transition ( ASB3 ), and airway hyperreactivity and remodeling ( FBN3 , RECK ), and several were linked to asthma in genome- (e.g., MRPL14 , ASB3 ) or epigenome-wide association studies ( CLC , GPI , SSCRB4 , STRN4 ). Signaling pathways inferred from the co-expression pattern were associated with airway remodeling (e.g., TGF-β/Smad2/3, E2F/Rb, and Wnt/β-catenin).
Keyphrases
- epithelial mesenchymal transition
- gene expression
- end stage renal disease
- chronic obstructive pulmonary disease
- poor prognosis
- single cell
- lung function
- computed tomography
- dna methylation
- signaling pathway
- immune response
- genome wide
- ejection fraction
- transforming growth factor
- cross sectional
- cell migration
- chronic kidney disease
- stem cells
- peritoneal dialysis
- newly diagnosed
- cell adhesion
- reactive oxygen species
- prognostic factors
- rna seq
- chronic rhinosinusitis
- magnetic resonance imaging
- allergic rhinitis
- machine learning
- binding protein
- patient reported outcomes
- long non coding rna
- cystic fibrosis
- early onset
- positron emission tomography
- patient reported
- optical coherence tomography
- inflammatory response
- endoplasmic reticulum stress
- deep learning
- contrast enhanced
- image quality