Expression of cilium-associated genes defines novel molecular subtypes of idiopathic pulmonary fibrosis
- PMID: 23783374
- PMCID: PMC7138412
- DOI: 10.1136/thoraxjnl-2012-202943
Expression of cilium-associated genes defines novel molecular subtypes of idiopathic pulmonary fibrosis
Abstract
Background: Idiopathic pulmonary fibrosis (IPF) is an untreatable lung disease with a median survival of only 3-5 years that is diagnosed using a combination of clinical, radiographic and pathologic criteria. Histologically, IPF is characterised by usual interstitial pneumonia (UIP), a fibrosing interstitial pneumonia with a pattern of heterogeneous, subpleural regions of fibrotic and remodelled lung. We hypothesised that gene expression profiles of lung tissue may identify molecular subtypes of disease that could classify subtypes of IPF/UIP that have clinical implications.
Methods and findings: We collected transcriptional profiles on lung tissue from 119 patients with IPF/UIP and 50 non-diseased controls. Differential expression of individual transcripts was identified using an analysis of covariance (ANCOVA) model incorporating the clinical diagnosis of each patient as well as age, gender and smoking status. Validation was performed in an independent cohort of 111 IPF/UIP and 39 non-diseased controls. Our analysis identified two subtypes of IPF/UIP based on a strong molecular signature associated with expression of genes previously associated with fibrosis (matrix metalloproteinases, osteopontin, keratins), cilium genes and genes with unknown function. We demonstrate that elevated expression of cilium genes is associated with more extensive microscopic honeycombing and higher expression of both the airway mucin gene MUC5B and the metalloproteinase MMP7, a gene recently implicated in attenuating ciliated cell differentiation during wound repair.
Conclusions: Expression of cilium genes appears to identify two unique molecular phenotypes of IPF/UIP. The different molecular profiles may be relevant to therapeutic responsiveness in patients with IPF/UIP.
Keywords: Interstitial Fibrosis.
Conflict of interest statement
Figures
Comment in
-
IPF: time for the (ciliary) beat generation?Thorax. 2013 Dec;68(12):1088-9. doi: 10.1136/thoraxjnl-2013-203928. Epub 2013 Sep 4. Thorax. 2013. PMID: 24005445 No abstract available.
Similar articles
-
The idiopathic pulmonary fibrosis honeycomb cyst contains a mucocilary pseudostratified epithelium.PLoS One. 2013;8(3):e58658. doi: 10.1371/journal.pone.0058658. Epub 2013 Mar 20. PLoS One. 2013. PMID: 23527003 Free PMC article.
-
Molecular markers of telomere dysfunction and senescence are common findings in the usual interstitial pneumonia pattern of lung fibrosis.Histopathology. 2021 Jul;79(1):67-76. doi: 10.1111/his.14334. Epub 2021 Apr 14. Histopathology. 2021. PMID: 33432658 Free PMC article.
-
IPF: time for the (ciliary) beat generation?Thorax. 2013 Dec;68(12):1088-9. doi: 10.1136/thoraxjnl-2013-203928. Epub 2013 Sep 4. Thorax. 2013. PMID: 24005445 No abstract available.
-
Pathologic Criteria for the Diagnosis of Usual Interstitial Pneumonia vs Fibrotic Hypersensitivity Pneumonitis in Transbronchial Cryobiopsies.Mod Pathol. 2023 Sep;36(9):100221. doi: 10.1016/j.modpat.2023.100221. Epub 2023 May 24. Mod Pathol. 2023. PMID: 37236510 Review.
-
Idiopathic Pulmonary Fibrosis Is a Genetic Disease Involving Mucus and the Peripheral Airways.Ann Am Thorac Soc. 2018 Nov;15(Suppl 3):S192-S197. doi: 10.1513/AnnalsATS.201802-144AW. Ann Am Thorac Soc. 2018. PMID: 30431344 Free PMC article. Review.
Cited by
-
Role of telomere dysfunction and immune infiltration in idiopathic pulmonary fibrosis: new insights from bioinformatics analysis.Front Genet. 2024 Sep 13;15:1447296. doi: 10.3389/fgene.2024.1447296. eCollection 2024. Front Genet. 2024. PMID: 39346776 Free PMC article.
-
Construction of an artificial neural network diagnostic model and investigation of immune cell infiltration characteristics for idiopathic pulmonary fibrosis.BMC Pulm Med. 2024 Sep 17;24(1):458. doi: 10.1186/s12890-024-03249-6. BMC Pulm Med. 2024. PMID: 39289672 Free PMC article.
-
Adiponectin suppresses stiffness-dependent, profibrotic activation of lung fibroblasts.Am J Physiol Lung Cell Mol Physiol. 2024 Oct 1;327(4):L487-L502. doi: 10.1152/ajplung.00037.2024. Epub 2024 Aug 6. Am J Physiol Lung Cell Mol Physiol. 2024. PMID: 39104319 Free PMC article.
-
MUC5B Idiopathic Pulmonary Fibrosis Risk Variant Promotes a Mucosecretory Phenotype and Loss of Small Airway Secretory Cells.Am J Respir Crit Care Med. 2024 Aug 15;210(4):517-521. doi: 10.1164/rccm.202311-2111LE. Am J Respir Crit Care Med. 2024. PMID: 38924494 No abstract available.
-
Plausible role of INPP4A dysregulation in idiopathic pulmonary fibrosis.Physiol Rep. 2024 May;12(9):e16032. doi: 10.14814/phy2.16032. Physiol Rep. 2024. PMID: 38720166 Free PMC article.
References
-
- King T, Costabel U, Cordier J-F, et al. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med 2000;161(2 Pt 1):646–64. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials