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Chemokine expression in the early response to injury in human airway epithelial cells
- Source :
- PLoS ONE, Vol 13, Iss 3, p e0193334 (2018), PLoS ONE
- Publication Year :
- 2018
- Publisher :
- Public Library of Science (PLoS), 2018.
-
Abstract
- Basal airway epithelial cells (AEC) constitute stem/progenitor cells within the central airways and respond to mucosal injury in an ordered sequence of spreading, migration, proliferation, and differentiation to needed cell types. However, dynamic gene transcription in the early events after mucosal injury has not been studied in AEC. We examined gene expression using microarrays following mechanical injury (MI) in primary human AEC grown in submersion culture to generate basal cells and in the air-liquid interface to generate differentiated AEC (dAEC) that include goblet and ciliated cells. A select group of ~150 genes was in differential expression (DE) within 2–24 hr after MI, and enrichment analysis of these genes showed over-representation of functional categories related to inflammatory cytokines and chemokines. Network-based gene prioritization and network reconstruction using the PINTA heat kernel diffusion algorithm demonstrated highly connected networks that were richer in differentiated AEC compared to basal cells. Similar experiments done in basal AEC collected from asthmatic donor lungs demonstrated substantial changes in DE genes and functional categories related to inflammation compared to basal AEC from normal donors. In dAEC, similar but more modest differences were observed. We demonstrate that the AEC transcription signature after MI identifies genes and pathways that are important to the initiation and perpetuation of airway mucosal inflammation. Gene expression occurs quickly after injury and is more profound in differentiated AEC, and is altered in AEC from asthmatic airways. Our data suggest that the early response to injury is substantially different in asthmatic airways, particularly in basal airway epithelial cells.
- Subjects :
- 0301 basic medicine
Chemokine
Time Factors
Physiology
Cellular differentiation
Gene Identification and Analysis
Gene Expression
lcsh:Medicine
Genetic Networks
Pathology and Laboratory Medicine
Epithelium
Animal Cells
Immune Physiology
Gene expression
Medicine and Health Sciences
lcsh:Science
Immune Response
Innate Immune System
Multidisciplinary
biology
Chemotaxis
Cell Differentiation
Genomics
respiratory system
Cell biology
Trachea
Cell Motility
Cytokines
Chemokines
Cellular Types
Anatomy
medicine.symptom
Transcriptome Analysis
Network Analysis
Signal Transduction
Research Article
Computer and Information Sciences
Cell type
Immunology
education
Bronchi
Inflammation
Proinflammatory cytokine
03 medical and health sciences
Signs and Symptoms
Diagnostic Medicine
Genetics
medicine
Humans
Progenitor cell
Gene
Mechanical Phenomena
Gene Expression Profiling
lcsh:R
Biology and Life Sciences
Computational Biology
Epithelial Cells
Cell Biology
Molecular Development
Genome Analysis
Asthma
Biological Tissue
030104 developmental biology
Immune System
biology.protein
lcsh:Q
Developmental Biology
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- PLOS ONE
- Accession number :
- edsair.doi.dedup.....1bb8c0e8d20a60ad8e37a3b8e0258b04
- Full Text :
- https://doi.org/10.1371/journal.pone.0193334