Adenovirus vector-mediated YKL-40 shRNA attenuates eosinophil airway inflammation in a murine asthmatic model
Adenovirus vector-mediated YKL-40 shRNA attenuates eosinophil airway inflammation in a murine asthmatic model
复制标题
DOI：
10.1038/s41434-020-00202-0
复制
发表时间：
2020-10
期刊：
影响因子：
5.1
通讯作者：
Ling Wang;A. Bao;Ying Zheng;Aying Ma;Yi Wu;Huanxia Shang;Danruo Fang;Suqin Ben
中科院分区：
文献类型：
--
作者：
Ling Wang;A. Bao;Ying Zheng;Aying Ma;Yi Wu;Huanxia Shang;Danruo Fang;Suqin Ben
最近的研究表明，YKL-40参与了哮喘的发病机制。然而，其具体机制尚不清楚。本研究旨在探讨腺病毒载体介导的YKL-40短发夹RNA（shRNA）对哮喘小鼠气道炎症的调节作用。测定小鼠气道高反应性（AHR）、支气管肺泡灌洗液（BALF）中总白细胞和嗜酸性粒细胞百分比。采用实时定量PCR和Western blot检测YKL-40 mRNA和蛋白表达水平。采用酶联免疫吸附法（ELISA）检测BALF和血清中YKL-40和嗜酸性粒细胞相关趋化因子的表达水平。肺组织病理学检查观察哮喘小鼠气道周围炎性细胞浸润程度及气道粘液分泌情况，YKL-40 shRNA能显著抑制哮喘小鼠YKL-40基因表达。此外，YKL-40 shRNA可减轻哮喘小鼠模型的嗜酸性气道炎症、AHR、气道粘液分泌，并降低BALF和血清中YKL-40的水平。哮喘小鼠肺组织IL-5、IL-13、BALF和血清中Eotaxin、GM-CSF水平及mRNA表达均显著降低。骨髓信号分子包括IL-5、嗜酸性粒细胞趋化因子和GM-CSF与YKL-40水平降低相关。该研究表明，YKL-40可能通过改变骨髓信号分子参与哮喘炎症。YKL-40基因的RNA干扰可能为哮喘的治疗提供新的策略。
Recent studies have revealed that YKL-40 is involved in the pathogenesis of asthma. However, its specific mechanism remains unclear. The present study aims to investigate the effect of adenovirus vector-mediated YKL-40 short hairpin RNA (shRNA) on regulation of airway inflammation in a murine asthmatic model. Mice were assessed for airway hyperresponsiveness (AHR), total leukocytes and the percentage of eosinophil cells in bronchoalveolar lavage fluid (BALF). YKL-40 mRNA and protein expression levels were detected using quantitative real-time PCR and western blot assays. Enzyme-linked immunosorbent assay (ELISA) was used to detect YKL-40 and eosinophil-related chemokine expression levels in BALF and serum. Lung histology analyses were performed to evaluate the degree of inflammatory cell infiltration around the airway and airway mucus secretion.YKL-40 shRNA significantly inhibited the YKL-40 gene expression in asthmatic mice. In addition, YKL-40 shRNA alleviated eosinophilic airway inflammation, AHR, airway mucus secretion and decreased the levels of YKL-40 in BALF and serum in a murine asthmatic model. The levels and mRNA expression of IL-5, IL-13 in asthmatic mice lung tissues, eotaxin, and GM-CSF in BALF and serum significantly decreased. Bone marrow signaling molecules including IL-5, eotaxin, and GM-CSF were correlated with decreased levels of YKL-40. The study reveals that YKL-40 could be involved in asthma inflammation by altering bone marrow signaling molecules. YKL-40 gene RNA interference could provide new therapeutic strategies for asthma.