MicroRNAs Associated with Chronic Mucus Hypersecretion in COPD Are Involved in Fibroblast-Epithelium Crosstalk.

Autor: Tasena H; Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands.; Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands.; Healthy Longevity Translational Research Program, National University of Singapore, Singapore 117596, Singapore.; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore., Timens W; Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands.; Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands., van den Berge M; Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands.; Department of Pulmonary Diseases, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands., van Broekhuizen J; Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands.; Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands., Kennedy BK; Healthy Longevity Translational Research Program, National University of Singapore, Singapore 117596, Singapore.; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.; Agency for Science, Technology and Research (A*STAR), Singapore Institute for Clinical Sciences, Singapore 117596, Singapore.; Centre for Healthy Ageing, National University Health System, National University of Singapore, Singapore 117596, Singapore., Hylkema MN; Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands.; Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands., Brandsma CA; Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands.; Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands., Heijink IH; Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands.; Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands.; Department of Pulmonary Diseases, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands.
Jazyk: angličtina
Zdroj: Cells [Cells] 2022 Feb 02; Vol. 11 (3). Date of Electronic Publication: 2022 Feb 02.
DOI: 10.3390/cells11030526
Abstrakt: We recently identified microRNAs (miRNAs) associated with chronic mucus hypersecretion (CMH) in chronic obstructive pulmonary disease (COPD), which were expressed in both airway epithelial cells and fibroblasts. We hypothesized that these miRNAs are involved in communication between fibroblasts and epithelium, contributing to airway remodeling and CMH in COPD. Primary bronchial epithelial cells (PBECs) differentiated at the air-liquid interface, and airway fibroblasts (PAFs) from severe COPD patients with CMH were cultured alone or together. RNA was isolated and miRNA expression assessed. miRNAs differentially expressed after co-culturing were studied functionally using overexpression with mimics in mucus-expressing human lung A549 epithelial cells or normal human lung fibroblasts. In PBECs, we observed higher miR-708-5pexpression upon co-culture with fibroblasts, and miR-708-5p expression decreased upon mucociliary differentiation. In PAFs, let-7a-5p, miR-31-5p and miR-146a-5p expression was significantly increased upon co-culture. miR-708-5p overexpression suppressed mucin 5AC (MUC5AC) secretion in A549, while let-7a-5poverexpression suppressed its target gene COL4A1 in lung fibroblasts. Our findings suggest that let-7a-5p, miR-31-5p and miR-146a-5p may be involved in CMH via fibroblasts-epithelium crosstalk, including extracellular matrix gene regulation, while airway epithelial expression of miR-708-5p may be involved directly, regulating mucin production. These findings shed light on miRNA-mediated mechanisms underlying CMH, an important symptom in COPD.
Databáze: MEDLINE
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