title: Effects of miRNA-145 on airway smooth muscle cells function.
abstract: The pathological changes of airway smooth muscle (ASM) contribute to airway remodeling during asthma. Here, we investigated the effect of miR-145 on ASM function. We found that miR-145 was aberrantly more highly expressed in ASM cells exposed to cytokine stimulation that mimic the airway conditions of patients with asthma. Repression of miR-145 resulted in decreased ASM cell proliferation and migration in a dose-dependent manner and down-regulation of type I collagen and contractile protein MHC in ASM cells. qRT-PCR and Western blot analysis demonstrated that miR-145 negatively regulated the expression of downstream target Krüppel-like factor 4 (KLF4) protein, and overexpression of KLF4 attenuated the effects of miR-145 on ASM cells. Further studies showed that KLF4 significantly up-regulated the expression of p21 and down-regulated matrix metalloproteinase (MMP-2 and MMP-9). In conclusion, miR-145 overexpression in ASM cells significantly inhibited KLF4, and subsequently affected downstream p21, MMP-2, and MMP-9 expressions, eventually leading to enhanced proliferation and migration of ASM cells in vitro.
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University Medical College, 157 Xiwu Road, Xi'an Shaanxi, 710004, China. yunliusx@163.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University Medical College, 157 Xiwu Road, Xi'an Shaanxi, 710004, China.
authors.forename: Xiuzhen
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University Medical College, 157 Xiwu Road, Xi'an Shaanxi, 710004, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University Medical College, 157 Xiwu Road, Xi'an Shaanxi, 710004, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Fang
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University Medical College, 157 Xiwu Road, Xi'an Shaanxi, 710004, China.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University Medical College, 157 Xiwu Road, Xi'an Shaanxi, 710004, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University Medical College, 157 Xiwu Road, Xi'an Shaanxi, 710004, China.
authors.forename: Manxiang
authors.initials: M
authors.lastname: Li
mesh_terms: D056151:Airway Remodeling / Q000235:genetics / Q000502:physiology; D001249:Asthma / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis; D003285:Contractile Proteins / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis*; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D035683:MicroRNAs / Q000235:genetics*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000096:biosynthesis
chemical_list: C493956:CDKN1A protein, human; D024042:Collagen Type I; D003285:Contractile Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D018995:Myosin Heavy Chains
keywords: Airway remodeling; Airway smooth muscle cells; KLF4; MMP-2; miRNA-145; p21