title: 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.
abstract: 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.
authors.affiliation: The Second Department of Respiratory Internal Medicine, Xi'an Children's Hospital, Xi'an 710003, Shaanxi, PR China; Department of Oncology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi, PR China. Electronic address: weichengxa@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Department of General Surgery, the Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710004, Shaanxi, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yan
authors.affiliation: Department of Nephropathy, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi, PR China. Electronic address: liyixielyx@163.com.
authors.forename: Li-Yi
authors.initials: LY
authors.lastname: Xie
authors.affiliation: Department of Internal Medicine, Xi'an Children's Hospital, Xi'an 710003,Shaanxi, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, Xi'an Children's Hospital, Xi'an 710003,Shaanxi, PR China.
authors.forename: Hong-Chuan
authors.initials: HC
authors.lastname: Yu
authors.affiliation: Department of Internal Medicine, Xi'an Children's Hospital, Xi'an 710003,Shaanxi, PR China.
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Huang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi, PR China.
authors.forename: Cheng-Xue
authors.initials: CX
authors.lastname: Dang
mesh_terms: D000328:Adult; D056151:Airway Remodeling / Q000276:immunology*; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015153:Blotting, Western; D001980:Bronchi / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000276:immunology* / Q000378:metabolism; D009130:Muscle, Smooth / Q000276:immunology / Q000473:pathology; D050778:NFATC Transcription Factors / Q000096:biosynthesis* / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000276:immunology / Q000378:metabolism
chemical_list: C542359:MIRN143 microRNA, human; D035683:MicroRNAs; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; D053773:Transforming Growth Factor beta1
keywords: Asthma; Cell proliferation; Extracellular matrix production (ECM); MiR-143-3p; The nuclear factor of activated T cells 1 (NFATc1)