Targeted inhibition of Six1 attenuates allergic airway inflammation and remodeling in asthmatic mice

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• 作者：Zhao-Chuan Yang^a ; Ming-Ji Yi^a ; Yan-Chun Shan^a ; Chong Wang^b ; Ni Ran^a ; Li-Ying Jin^c ; Peng Fu^a ; Xue-Ying Feng^a ; Lei Xu^b ; Zheng-Hai Qu^b ; ^{quzhenghai@163.com}
• 关键词：Asthma ; Six1 ; Airway inflammation ; Airway remodeling ; Nuclear factor kB
• 刊名：Biomedicine & Pharmacotherapy
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：84
• 期：Complete
• 页码：1820-1825
• 全文大小：2028 K
• 卷排序：84

文摘

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.