Journal
JOURNAL OF ASTHMA
Volume 56, Issue 4, Pages 341-349Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/02770903.2018.1455859
Keywords
MicroRNA-21 ' transforming growth factor beta; TGF beta signaling; airway remodeling; human bronchial fibroblasts
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Funding
- Natural Science Foundation of Jiangsu Province [BK20151112]
- Medical Innovation Team of Jiangsu Province [CXTDB2017016]
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Objective: Airway remodeling is an important pathological feature of asthma. Excessive deposition of extracellular matrix (e.g., collagen) secreted from fibroblasts is a major factor contributing to airway remodeling. Currently, the mechanism by which collagen continues to be oversynthesized in the airway remains unclear. In this study, we investigated the role of the microRNA-21 (miR-21) and TGF beta/Smad signaling pathway in human bronchial fibroblasts (HBFs), and explored the regulatory mechanism of airway remodeling. Methods: HBFs were cultured in vitro and treated with the transforming growth factor beta (TGF beta), receptor inhibitor (SB431542), and TGF beta 1. miR-21 and Smad7 overexpressing lentiviruses, as well as an miR-21 interfering lentivirus were constructed and transfected into HBFs. Western blotting was used to determine the expression of airway remodeling-related proteins and proteins in the TGF beta/Smad signaling pathway. miR-21 expression was measured by quantitative real-time PCR. Results: The high expression of miR-21 induced by TGF beta 1 was reduced following the treatment with the SB431542 in HBFs. Smad7 overexpression inhibited the elevated expression of the COL I protein induced by miR-21 overexpression in HBFs. Inhibiting miR-21 expression upregulated the level of Smad7 protein, thus reducing the expression of airway remodeling-related proteins induced by TGF beta 1 stimulation in HBFs. Conclusions: TGF beta 1 can induce miR-21 expression in HBFs through the TGF beta/Smad signaling pathway to promote airway remodeling. miR-21 downregulates Smad7, activates the TGF beta/Smad signaling pathway, and promotes airway remodeling. Mutual regulation between miR-21 and the TGF beta/Smad signaling pathway in HBFs promotes airway remodeling.
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