Marked TGF-β-regulated miRNA expression changes in both COPD and control lung fibroblasts.

Autor: Ong J; University of Groningen, University Medical Centre Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands.; University of Groningen, University Medical Centre Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands., Faiz A; University of Groningen, University Medical Centre Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands.; University of Groningen, University Medical Centre Groningen, Department of Pulmonary Diseases, Groningen, The Netherlands.; University of Technology Sydney, Respiratory Bioinformatics and Molecular Biology (RBMB) Faculty of Science, Ultimo, NSW, 2007, Australia., Timens W; University of Groningen, University Medical Centre Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands.; University of Groningen, University Medical Centre Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands., van den Berge M; University of Groningen, University Medical Centre Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands.; University of Groningen, University Medical Centre Groningen, Department of Pulmonary Diseases, Groningen, The Netherlands., Terpstra MM; University of Groningen, University Medical Centre Groningen, Department of Genetics, Groningen, The Netherlands., Kok K; University of Groningen, University Medical Centre Groningen, Department of Genetics, Groningen, The Netherlands., van den Berg A; University of Groningen, University Medical Centre Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands., Kluiver J; University of Groningen, University Medical Centre Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands., Brandsma CA; University of Groningen, University Medical Centre Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands. c.a.brandsma@umcg.nl.; University of Groningen, University Medical Centre Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands. c.a.brandsma@umcg.nl.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2019 Dec 03; Vol. 9 (1), pp. 18214. Date of Electronic Publication: 2019 Dec 03.
DOI: 10.1038/s41598-019-54728-4
Abstrakt: COPD is associated with disturbed tissue repair, possibly due to TGF-β-regulated miRNA changes in fibroblasts. Our aim was to identify TGF-β-regulated miRNAs and their differential regulation and expression in COPD compared to control fibroblasts. Small RNA sequencing was performed on TGF-β-stimulated and unstimulated lung fibroblasts from 15 COPD patients and 15 controls. Linear regression was used to identify TGF-β-regulated and COPD-associated miRNAs. Interaction analysis was performed to compare miRNAs that responded differently to TGF-β in COPD and control. Re-analysis of previously generated Ago2-IP data and Enrichr were used to identify presence and function of potential target genes in the miRNA-targetome of lung fibroblasts. In total, 46 TGF-β-regulated miRNAs were identified in COPD and 86 in control fibroblasts (FDR < 0.05). MiR-27a-5p was the most significantly upregulated miRNA. MiR-148b-3p, miR-589-5p and miR-376b-3p responded differently to TGF-β in COPD compared to control (FDR < 0.25). MiR-660-5p was significantly upregulated in COPD compared to control (FDR < 0.05). Several predicted targets of miR-27a-5p, miR-148b-3p and miR-660-5p were present in the miRNA-targetome, and were mainly involved in the regulation of gene transcription. In conclusion, altered TGF-β-induced miRNA regulation and differential expression of miR-660-5p in COPD fibroblasts, may represent one of the mechanisms underlying aberrant tissue repair and remodelling in COPD.
Databáze: MEDLINE
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