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RNA-Sequencing of COPD ferret lung reveals uniquely expressed gene common to human COPD.

ABSTRACT: RNA-Sequencing of COPD ferret lung reveals uniquely expressed gene common to human COPD.

PROVIDER: PRJNA797474 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17624225_1.fastq.gz	Fastqsanger.gz
	SRR17624225_2.fastq.gz	Fastqsanger.gz
	SRR17624226_1.fastq.gz	Fastqsanger.gz
	SRR17624226_2.fastq.gz	Fastqsanger.gz
	SRR17624227_1.fastq.gz	Fastqsanger.gz

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RNA-Sequencing of COPD ferret lung reveals uniquely expressed gene common to human COPD.

Project description:Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease typified by not fully reversible and often progressive airflow obstruction, along with persistent respiratory symptoms. This gap is due to lack of animal models that more closely mimic human COPD are needed to bridge translational gaps. Commonly used mice model produces primarily emphysematous disease and do not develop features pathognomonic for chronic bronchitis. Suggesting the potential for additional molecular insights to be obtained from animal models that exhibit COPD with features of chronic bronchitis and emphysema, as in humans. We sought to identify whether our ferret model of COPD captures unique genetic signatures in comparison to mouse models that can help improve understanding of the molecular pathogenesis of COPD and promote the development of new and effective therapies.

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Comparative transcriptomics in human COPD reveals dysregulated genes uniquely expressed in ferrets.

Project description:BackgroundChronic obstructive pulmonary disease (COPD) is a progressive lung disease with poor treatment options. However, most mouse models of COPD produce a primarily emphysematous disease not recapitulating clinically meaningful COPD features like chronic bronchitis.MethodsWild-type ferrets (Mustela putorius furo) were divided randomly into two groups: whole body cigarette smoke exposure and air controls. Ferrets were exposed to smoke from 1R6F research cigarettes, twice daily for six months. RNA-sequencing was performed on RNA isolated from lung tissue. Comparative transcriptomics analyses of COPD in ferrets, mice, and humans were done to find the uniquely expressed genes. Further, Real-time PCR was performed to confirmed RNA-Seq data on multiple selected genes.ResultsRNA-sequence analysis identified 420 differentially expressed genes (DEGs) that were associated with the development of COPD in ferrets. By comparative analysis, we identified 25 DEGs that are uniquely expressed in ferrets and humans, but not mice. Among DEGs, a number were related to mucociliary clearance (NEK-6, HAS1, and KL), while others have been correlated with abnormal lung function (IL-18), inflammation (TREM1, CTSB), or oxidative stress (SRX1, AHRR). Multiple cellular pathways were aberrantly altered in the COPD ferret model, including pathways associated with COPD pathogenesis in humans. Validation of these selected unique DEGs using real-time PCR demonstrated > absolute 2-fold changes in mRNA versus air controls, consistent with RNA-seq analysis.ConclusionCigarette smoke-induced COPD in ferrets modulates gene expression consistent with human COPD and suggests that the ferret model may be uniquely well suited for the study of aspects of the disease.

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Project description:70 miRNAs and 2667 mRNAs were differentially expressed between lung tissue from subjects with COPD and smokers without COPD. miRNA and mRNA expression profiles enriched for biological pathways that may be relevant to the pathogenesis of COPD including the transforming growth factor b, Wnt and focal adhesion pathways. miR-223 and miR-1274a were the most affected miRNAs in subjects with COPD compared with smokers without obstruction. miR-15b was increased in COPD samples compared with smokers without obstruction and localised to both areas of emphysema and fibrosis. miR-15b was differentially expressed within GOLD classes of COPD. Expression of SMAD7, which was validated as a target for miR-15b, was decreased in bronchial epithelial cells in COPD.

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