The pathogenesis of asthma is closely related to histone acetylation modification, but the specific acetylation sites related to this process remain indistinct. Herein, our study sought to identify differentially modified acetylation sites and their expression distribution in cells involved in asthma in lung tissues. The airway hyper-responsiveness, inflammation, and remodeling were assessed by non-invasive whole-body plethysmography, ELISA, and hematoxylin-eosin staining to confirm the successful establishment of the allergic asthma model. Afterward, the differentially modified acetylation sites in asthmatic lung tissues were identified and validated by using proteomics and western blotting, respectively. The immunohistochemistry analysis was applied to reveal the distribution of identified acetylation sites in asthmatic lung tissues. A total of 15 differentially modified acetylation sites, including 13 upregulated (H3K9ac, H3K14ac, H3K18ac, H3K23ac,H3K27ac, H3K36ac, H2B1KK120ac, H2B2BK20ac, H2BK16ac, H2BK20ac, H2BK108ac, H2BK116ac, and H2BK120ac) and 2 downregulated (H2BK5ac and H2BK11ac) sites were identified and validated. Furthermore, immunohistochemical staining of lung tissues showed that nine of the identified histone acetylation sites (H2BK5, H2BK11, H3K18, H2BK116, H2BK20, H2BK120, H3K9, H3K36, and H3K27) were differentially expressed in airway epithelial cells, and the acetylation of identified H3 histones were observed in both eosinophil and perivascular inflammatory cells. Additionally, differential expression of histone acetylation sites was also observed in nucleus of airway epithelial cells, vascular smooth muscle cells, perivascular inflammatory cells, and airway smooth muscle cells. In conclusion, we identified potential acetylation sites associated with asthma pathogenesis. These findings may contribute greatly in the search for therapeutic approaches for allergic asthma.

哮喘的发病机制与组蛋白乙酰化修饰密切相关，但与该过程相关的具体乙酰化位点仍不清楚。在此，我们的研究试图确定差异修饰的乙酰化位点及其在肺组织哮喘相关细胞中的表达分布。通过无创全身体积描记法、ELISA和苏木精-伊红染色评估气道高反应性、炎症和重塑，以确认过敏性哮喘模型的成功建立。之后，分别使用蛋白质组学和蛋白质印迹鉴定和验证哮喘肺组织中差异修饰的乙酰化位点。应用免疫组织化学分析来揭示哮喘肺组织中已识别的乙酰化位点的分布。总共15位差异改性的乙酰化位点，包括13个上调（H3K9Ac，H3K14Ac，H3K18Ac，H3K23Ac，H3K27Ac，H3K36Ac，H2B1K120Ac，H2B2BK20Ac，H2BK16Ac，H2BK20Ac，H2BK108Ac，H2BK116Ac和H2BK120Ac）和2个下调（H2BK5AC和H2BK11Ac）位点识别和验证。此外，肺组织的免疫组化染色显示，9 个已鉴定的组蛋白乙酰化位点（H2BK5、H2BK11、H3K18、H2BK116、H2BK20、H2BK120、H3K9、H3K36 和 H3K27）在气道上皮细胞中差异表达，鉴定出的 H3在嗜酸性粒细胞和血管周围炎症细胞中均观察到组蛋白。此外，组蛋白乙酰化位点在气道上皮细胞核、血管平滑肌细胞、血管周围炎症细胞、和气道平滑肌细胞。总之，我们确定了与哮喘发病机制相关的潜在乙酰化位点。这些发现可能有助于寻找过敏性哮喘的治疗方法。