MiR-143-3p controls TGF-β1-induced cell proliferation and extracellular matrix production in airway smooth muscle via negative regulation of the nuclear factor of activated T cells 1

•MiR-143-3p is aberrantly expressed in ASMCs stimulated with TGF- β1.•The effect of miR-143-3p on TGF-β1-induced proliferation and ECM production in ASMCs.•NFATc1 is identified as a directly target of miR-143-3p.•NFATc1 abrogates inhibition effects of miR-143-3p on TGF-β1-induced ASMCs. MicroRNAs (m...

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Published in:Molecular immunology 2016-10, Vol.78, p.133-139
Main Authors: Cheng, Wei, Yan, Kun, Xie, Li-Yi, Chen, Feng, Yu, Hong-Chuan, Huang, Yan-Xia, Dang, Cheng-Xue
Format: Article
Language:English
Subjects:
Adult
Airway Remodeling - immunology
Asthma
Asthma - genetics
Asthma - immunology
Asthma - pathology
Blotting, Western
Bronchi - immunology
Bronchi - metabolism
Bronchi - pathology
Cell proliferation
Cell Proliferation - physiology
Cells, Cultured
Down-Regulation
Enzyme-Linked Immunosorbent Assay
Extracellular Matrix - pathology
Extracellular matrix production (ECM)
Female
Gene Expression Regulation - immunology
Humans
Male
MicroRNAs - immunology
MicroRNAs - metabolism
MiR-143-3p
Muscle, Smooth - immunology
Muscle, Smooth - pathology
NFATC Transcription Factors - biosynthesis
NFATC Transcription Factors - immunology
Real-Time Polymerase Chain Reaction
The nuclear factor of activated T cells 1 (NFATc1)
Transforming Growth Factor beta1 - immunology
Transforming Growth Factor beta1 - metabolism
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Summary:•MiR-143-3p is aberrantly expressed in ASMCs stimulated with TGF- β1.•The effect of miR-143-3p on TGF-β1-induced proliferation and ECM production in ASMCs.•NFATc1 is identified as a directly target of miR-143-3p.•NFATc1 abrogates inhibition effects of miR-143-3p on TGF-β1-induced ASMCs. MicroRNAs (miRNAs) are small noncoding RNAs that function in diverse biological processes. However, little is known about the precise role of microRNAs in the functioning of airway smooth muscle cells (ASMCs). Here, we investigated the potential role and mechanisms of the miR-143 -3p on proliferation and the extracellular matrix (ECM) protein production of ASMCs. We demonstrated that miR-143-3p was aberrantly lower in ASMCs isolated from individuals with asthma than in individuals without asthma. Meanwhile, TGF-β1 caused a marked decrease in a time-dependent manner in miR-143-3p expression in ASMCs from asthmatics. Additionally, the overexpression of miR- 143-3p robustly reduced TGF-β1-induced ASMCs proliferation and downregulated CDK and cyclin expression, whereas the inhibition of miR-143-3p significantly enhanced ASMCs proliferation and upregulated the level of CDKs and cyclins. Re-expression of miR-143-3p attenuated ECM protein deposition reflected as a marked decrease in the expression of type I collagen and fibronectin, whereas miR-143-3p downregulation caused an opposite effect on the expression of type I collagen and fibronectin. Moreover, qRT-PCR and western blot analysis indicated that miR-143-3p negatively regulated the expression of nuclear factor of activated T cells 1 (NFATc1). Subsequent analyses demonstrated that NFATc1 was a direct and functional target of miR-143-3p, which was validated by the dual luciferase reporter assay. Most importantly, the overexpression of NFATc1 effectively reversed the inhibition of miR-143-3p on TGF-β1-induced proliferation, and strikingly abrogated the effect of miR-143-3p on the expression of CDK4 and Cyclin D1. Together, miR-143-3p may function as an inhibitor of asthma airway remodeling by suppressing proliferation and ECM protein deposition in TGF-β1-mediated ASMCs via the negative regulation of NFATc1 signaling, suggesting miR-143-3p as a potential therapeutic target for asthma.
ISSN:0161-5890
1872-9142
DOI:10.1016/j.molimm.2016.09.004