title: Targeted inhibition of Six1 attenuates allergic airway inflammation and remodeling in asthmatic mice.
abstract: Asthma is an inflammatory disease of the airways, characterized by lung eosinophilia, mucus hypersecretion by goblet cells and airway hyperresponsiveness to inhaled allergens. The purpose of this study was to evaluate the effects of Six1 on airway inflammation and remodeling and the underlying mechanisms in a murine model of chronic asthma. Female BALB/c mice were randomly divided into four groups: phosphate-buffered saline control, ovalbumin (OVA)-induced asthma group, OVA+siNC and OVA+siSix1. In this mice model, Six1 expression level was significantly elevated in OVA-induced asthma of mice. Additionally, downregulation of Six1 dramatically decreased OVA-challenged inflammation, infiltration, and mucus production. Moreover, silencing of Six1 resulted in decreased levels of immunoglobulin E and inflammatory mediators and reduced inflammatory cell accumulation, as well as inhibiting the expression of important mediators including matrix metalloproteinase MMP-2 and MMP-9, which is related to airway remodeling. Further analysis indicated that silencing of Six1 can significantly inhibit NF-kB pathway activation in the lungs. .In conclusion, these findings indicated that the downregulation of Six1 effectively inhibited airway inflammation and reversed airway remodeling, which suggest that Six1 represents a promising therapeutic strategy for human allergic asthma.
authors.affiliation: Department of Child Health Care, The Affiliated Hospital of Qingdao University, Qingdao 266003, PR China.
authors.forename: Zhao-Chuan
authors.initials: ZC
authors.lastname: Yang
authors.affiliation: Department of Child Health Care, The Affiliated Hospital of Qingdao University, Qingdao 266003, PR China.
authors.forename: Ming-Ji
authors.initials: MJ
authors.lastname: Yi
authors.affiliation: Department of Child Health Care, The Affiliated Hospital of Qingdao University, Qingdao 266003, PR China.
authors.forename: Yan-Chun
authors.initials: YC
authors.lastname: Shan
authors.affiliation: Department of Pediatrics, The Affiliated Hospital of Qingdao University, Qingdao 266003, PR China.
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Child Health Care, The Affiliated Hospital of Qingdao University, Qingdao 266003, PR China.
authors.forename: Ni
authors.initials: N
authors.lastname: Ran
authors.affiliation: Cerebrovascular Disease Research Institute, The Affiliated Hospital of Qingdao University, Qingdao 266003, PR China.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Jin
authors.affiliation: Department of Child Health Care, The Affiliated Hospital of Qingdao University, Qingdao 266003, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Fu
authors.affiliation: Department of Child Health Care, The Affiliated Hospital of Qingdao University, Qingdao 266003, PR China.
authors.forename: Xue-Ying
authors.initials: XY
authors.lastname: Feng
authors.affiliation: Department of Pediatrics, The Affiliated Hospital of Qingdao University, Qingdao 266003, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Pediatrics, The Affiliated Hospital of Qingdao University, Qingdao 266003, PR China. Electronic address: quzhenghai@163.com.
authors.forename: Zheng-Hai
authors.initials: ZH
authors.lastname: Qu
mesh_terms: D056151:Airway Remodeling; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007073:Immunoglobulin E / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D010047:Ovalbumin; D015398:Signal Transduction
chemical_list: D018398:Homeodomain Proteins; D018836:Inflammation Mediators; D016328:NF-kappa B; C490947:Six1 protein, mouse; D007073:Immunoglobulin E; D010047:Ovalbumin; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: Airway inflammation; Airway remodeling; Asthma; Nuclear factor kB; Six1