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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Cecchini, Matthew J. Hosein, Karishma Howlett, Christopher J. Joseph, Mariamma Mura, Marco |
| Abstract | Background The clinical-radiographic distinction between idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) is challenging. We sought to investigate the gene expression profiles of IPF and NSIP vs. normal controls. Methods Gene expression from explanted lungs of patients with IPF (n = 22), NSIP (n = 10) and from normal controls (n = 11) was assessed. Microarray analysis included Significance Analysis of Microarray (SAM), Ingenuity Pathway, Gene-Set Enrichment and unsupervised hierarchical clustering analyses. Immunohistochemistry and serology of proteins of interest were conducted. Results NSIP cases were significantly enriched for genes related to mechanisms of immune reaction, such as T-cell response and recruitment of leukocytes into the lung compartment. In IPF, in contrast, these involved senescence, epithelial-to-mesenchymal transition, myofibroblast differentiation and collagen deposition. Unlike the IPF group, NSIP cases exhibited a strikingly homogenous gene signature. Clustering analysis identified a subgroup of IPF patients with intermediate and ambiguous expression of SAM-selected genes, with the interesting upregulation of both NSIP-specific and senescence-related genes. Immunohistochemistry for p16, a senescence marker, on fibroblasts differentiated most IPF cases from NSIP. Serial serum levels of periostin, a senescence effector, predicted clinical progression in a cohort of patients with IPF. Conclusions Comprehensive gene expression profiling in explanted lungs identifies distinct transcriptional profiles and differentially expressed genes in IPF and NSIP, supporting the notion of NSIP as a standalone condition. Potential gene and protein markers to discriminate IPF from NSIP were identified, with a prominent role of senescence in IPF. The finding of a subgroup of IPF patients with transcriptional features of both NSIP and senescence raises the hypothesis that “senescent” NSIP may represent a risk factor to develop superimposed IPF. |
| Related Links | https://respiratory-research.biomedcentral.com/counter/pdf/10.1186/s12931-018-0857-1.pdf |
| Ending Page | 12 |
| Page Count | 12 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| DOI | 10.1186/s12931-018-0857-1 |
| Journal | Respiratory Research |
| Issue Number | 1 |
| Volume Number | 19 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2018-08-15 |
| Access Restriction | Open |
| Subject Keyword | Pneumology Respiratory System Idiopathic pulmonary fibrosis Usual interstitial pneumonia Non-specific interstitial pneumonia Microarray Pneumology/Respiratory System |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pulmonary and Respiratory Medicine |
| Journal Impact Factor | 4.7/2023 |
| 5-Year Journal Impact Factor | 5.3/2023 |
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