International Archives of Allergy and Immunology
Experimental Allergy – Research Article
MiR-204-5p Inhibits Transforming Growth Factor-β1-Induced Proliferation and Extracellular Matrix Production of Airway Smooth Muscle Cells by Regulating Six1 in AsthmaYang Z.a,b · Qu Z.c · Yi M.b · Lv Z.d · Wang Y.b · Shan Y.b · Ran N.b · Liu X.aaDepartment of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
bDepartment of Child Health Care, The Affiliated Hospital of Qingdao University, Qingdao, China cCenter of Pediatrics, The Affiliated Hospital of Qingdao University, Qingdao, China dBreast Center, The Affiliated Hospital of Qingdao University, Qingdao, China |
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Article / Publication Details
Received: November 01, 2019
Accepted: November 27, 2019
Published online: January 17, 2020
Issue release date: April 2020
Number of Print Pages: 10
Number of Figures: 9
Number of Tables: 0
ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)
For additional information: https://www.karger.com/IAA
Abstract
Background: Transforming growth factor-β1 (TGF-β1)-induced proliferation of airway smooth muscle cells plays critical roles in the development of airway remodeling. Six1 (sine oculis homeobox homolog 1) has been demonstrated to be involved in airway inflammation and remodeling in asthmatic mice. Objectives: The aim of this work was to investigate the potential role of miR-204-5p in the proliferation and extracellular matrix (ECM) production of airway smooth muscle cells in asthma. Methods: Real-time PCR was used to measure the expression of miR-204-5p in asthmatic airway smooth muscle cells. Cell viability and apoptosis were detected to evaluate the effect of miR-204-5p on airway smooth muscle cells. Dual-luciferase reporter experiments were applied to identify the target genes of miR-204-5p. Results: MiR-204-5p was downregulated notably in asthmatic airway smooth muscle cells as well as cells stimulated with TGF-β1. Overexpression of miR-204-5p markedly suppressed the TGF-β1-induced proliferation of airway smooth muscle cells and the deposition of ECM, whereas the inhibition of miR-204-5p significantly enhanced the proliferation of airway smooth muscle cells and upregulated the level of fibronectin and collagen III. Furthermore, subsequent analyses demonstrated that Six1 was a direct target of miR-204-5p, and Western blot further indicated that miR-204-5p negatively regulated the expression of Six1. Most importantly, the restoration of Six1 expression reversed the inhibitory effect of miR-204-5p on TGF-β1-induced proliferation and ECM production. Conclusions: MiR-204-5p inhibits TGF-β1-induced proliferation and ECM production of airway smooth muscle cells by regulating Six1, identifying a potential therapeutic target for preventing airway remodeling in asthma.
© 2020 S. Karger AG, Basel
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Article / Publication Details
Received: November 01, 2019
Accepted: November 27, 2019
Published online: January 17, 2020
Issue release date: April 2020
Number of Print Pages: 10
Number of Figures: 9
Number of Tables: 0
ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)
For additional information: https://www.karger.com/IAA
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