Evaluation of microRNA expression in a sheep model for lung fibrosis

Udari Eshani Perera,Kenneth J Snibson,Rukmali Wijayarathna,Andrew Stent,Habtamu B Derseh,Sasika N V Dewage

doi:10.1186/s12864-021-08073-4

Abstract

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic progressive fibroproliferative disorder that has one of the poorest prognoses amongst interstitial lung diseases. Recently, the finding of aberrant expression levels of miRNAs in IPF patients has drawn significant attention to the involvement of these molecules in the pathogenesis of this disease. Clarification of the differential expression of miRNAs in health and disease may identify novel therapeutic strategies that can be employed in the future to combat IPF. This study evaluates the miRNA expression profiles in a sheep model for lung fibrosis and compares them to the miRNA profiles of both IPF patients and the mouse bleomycin model for pulmonary fibrosis. Pathway enrichment analyses were performed on differentially expressed miRNAs to illustrate which biological mechanisms were associated with lung fibrosis.ResultsWe discovered 49 differentially expressed miRNAs in the sheep fibrosis model, in which 32 miRNAs were significantly down regulated, while 17 miRNAs were significantly upregulated due to bleomycin-induced lung injury. Moreover, the miRNA families miR-29, miR-26, miR-30, let-7, miR-21, miR-19, miR-17 and miR-199 were aberrantly expressed in both sheep and mouse models, with similar differential miRNAs expression observed in IPF cases. Importantly, 18 miRNAs were aberrantly expressed in both the sheep model and IPF patients, but not in mice.ConclusionTogether with pathway enrichment analyses, these results show that the sheep model can potentially be used to characterize previously unrecognized biological pathways associated with lung fibrosis.

Highlights

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibroproliferative disorder that has one of the poorest prognoses amongst interstitial lung diseases
Segmental lung compliance reduced when the lung fibrosis increases at week 4 Lung function was assessed by measuring the segmental compliance (Cseg) in saline- and bleomycin-infused lung lobes at baseline and week 4 (Fig. 1C)
We identified 7 miRNA families where upregulation was restricted to IPF patients and sheep lung fibrosis, and a different set of 6 miRNA families where the upregulation was restricted to IPF patients and mice (Table 2 and Fig. 4B)

Summary

Introduction

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibroproliferative disorder that has one of the poorest prognoses amongst interstitial lung diseases. The finding of aberrant expression levels of miRNAs in IPF patients has drawn significant attention to the involvement of these molecules in the pathogenesis of this disease. This study evaluates the miRNA expression profiles in a sheep model for lung fibrosis and compares them to the miRNA profiles of both IPF patients and the mouse bleomycin model for pulmonary fibrosis. Pathway enrichment analyses were performed on differentially expressed miRNAs to illustrate which biological mechanisms were associated with lung fibrosis. Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibroproliferative disorder categorized under the umbrella of interstitial lung diseases [1,2,3].

Methods

Results

Discussion

Conclusion