Transcriptomic profiling reveals disease-specific characteristics of epithelial cells in idiopathic pulmonary fibrosis.

Boesch, Maximilian; Baty, Florent; Brutsche, Martin H; Tamm, Michael; Roux, Julien; Knudsen, Lars; Gazdhar, Amiq; Geiser, Thomas; Khan, Petra; Hostettler, Katrin E (2020). Transcriptomic profiling reveals disease-specific characteristics of epithelial cells in idiopathic pulmonary fibrosis. Respiratory research, 21(1), p. 165. BioMed Central 10.1186/s12931-020-01414-z

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BACKGROUND

Idiopathic pulmonary fibrosis (IPF) is an incurable disease characterized by progressive lung fibrosis ultimately resulting in respiratory failure and death. Recurrent micro-injuries to the alveolar epithelium and aberrant alveolar wound healing with impaired re-epithelialization define the initial steps of the pathogenic trajectory. Failure of timely alveolar epithelial repair triggers hyper-proliferation of mesenchymal cells accompanied by increased deposition of extracellular matrix into the lung interstitium.

METHODS

We previously isolated fibrosis-specific mesenchymal stem cell (MSC)-like cells from lung tissue of patients with interstitial lung diseases. These cells produced factors bearing anti-fibrotic potential and changed their morphology from mesenchymal to epithelial upon culture in an epithelial cell (EC)-specific growth medium. Here, we set out to molecularly characterize these MSC-like cell-derived ECs using global gene expression profiling by RNA-sequencing. Moreover, we aimed at characterizing disease-specific differences by comparing the transcriptomes of ECs from IPF and non-IPF sources.

RESULTS

Our results suggest that differentially expressed genes are enriched for factors related to fibrosis, hypoxia, bacterial colonization and metabolism, thus reflecting many of the hallmark characteristics of pulmonary fibrosis. IPF-ECs showed enrichment of both pro- and anti-fibrotic genes, consistent with the notion of adaptive, compensatory regulation.

CONCLUSIONS

Our findings support the hypothesis of a functional impairment of IPF-ECs, which could possibly explain the poor clinical outcome of IPF that roughly compares to those of advanced-stage cancers. Our study provides a valuable resource for downstream mechanistic investigation and the quest for novel therapeutic IPF targets.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology

UniBE Contributor:

Gazdhar, Amiq and Geiser, Thomas

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1465-9921

Publisher:

BioMed Central

Language:

English

Submitter:

Anja Ebeling

Date Deposited:

08 Jul 2020 17:14

Last Modified:

28 Jul 2020 15:59

Publisher DOI:

10.1186/s12931-020-01414-z

PubMed ID:

32605572

Uncontrolled Keywords:

Epithelial cell Idiopathic pulmonary fibrosis Lung fibrosis Mesenchymal stem cell RNA-sequencing

BORIS DOI:

10.7892/boris.145084

URI:

https://boris.unibe.ch/id/eprint/145084

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