4.7 Article

MicroRNA-335-5p alleviates inflammatory response, airway fibrosis, and autophagy in childhood asthma through targeted regulation of autophagy related 5

Journal

BIOENGINEERED
Volume 13, Issue 1, Pages 1791-1801

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/21655979.2021.1996315

Keywords

Childhood asthma; MiR-335-5p; ATG5; inflammatory response; airway fibrosis; autophagy

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This study investigated the role and mechanism of miR-335-5p in the treatment of childhood asthma, and found that it can alleviate inflammation, airway fibrosis, and autophagy. This research has important implications for improving the treatment of childhood asthma.
Childhood asthma is the most universal chronic disease, with significant cases reported. Despite the current progress in treatment, prognosis remains poor and the existing drugs cause serious side effects. This investigation explored the mechanisms and use of miR-335-5p on childhood asthma therapy. MiR-335-5p and ATG5 expression was analyzed in clinical plasma samples through RT-qPCR. Airway smooth muscle cells (ASMCs) were cultured, and transfected with miR-335-5p mimic, miR-335-5p inhibitor, and pcDNA3.1-ATG5, or co-transfected with miR-335-5p mimic + pcDNA3.1-ATG5. Asthma cell models were constructed through TGF-beta 1, and animal models through ovalbumin (OVA). Monocyte-macrophage infiltration in bronchoalveolar lavage fluid (BALF) was determined by May-Grunwald-Giemsa staining, and collagen in lung tissue was assessed via Masson staining. Relationship between miR-335-5p and ATG5 was detected by dual-luciferase assay. Cell proliferation was detected by MTT assay. MiR-335-5p and ATG5 RNA expression was determined by RT-qPCR. Collagen I, collagen III, alpha-SMA, ATG5, LC3I/II, Beclin-1, and p62 protein expression levels in ASMCs were detected by western blot. MiR-335-5p expression was low, but ATG5 expression was high in childhood asthma. Versus OVA+ mimic NC group, the number of eosinophil and collagen in OVA+ miR-335-5p mimic group were reduced. In contrast to TGF-beta 1 + mimic NC group, TGF-beta 1 + miR-335-5p mimic group reduced inflammatory, airway fibrosis, and autophagy in ASMCs. ATG5 was miR-335-5p target. Overexpressing ATG5 significantly reversed the inhibitory effects of miR-335-5p on inflammatory response, fibrosis, and autophagy in ASMCs. Overall, the study concludes that MiR-335-5p alleviate inflammatory response, airway fibrosis, and autophagy in childhood asthma through targeted regulation of ATG5.

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