期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 180, 期 16, 页码 2156-2171出版社
WILEY
DOI: 10.1111/bph.16069
关键词
acute lung injury; chlorogenic acid; inflammatory cytokine; KAT2A; targeted inhibition
Respiratory diseases, such as acute lung injury (ALI), have become a global health problem. The excessive activation and recruitment of immunocytes in the lungs, as well as the release of cytokines, are considered the primary causes of ALI. However, the cellular mechanisms involved in ALI remain unknown. Therefore, new therapeutic strategies need to be developed to control inflammation and prevent the worsening of ALI.
Background and PurposeRespiratory diseases have become a global health problem and may lead to acute lung injury (ALI) in severe cases. ALI progression is associated with complex pathological changes; however, there are currently no effective therapeutic drugs. Excessive activation and recruitment of immunocytes in the lungs and the release of large amounts of cytokines are considered the primary causes of ALI, but the cellular mechanisms involved remain unknown. Therefore, new therapeutic strategies need to be developed to control the inflammatory response and prevent the further aggravation of ALI. Experimental ApproachLipopolysaccharide was administered to mice via tail vein injection to establish an ALI model. Key genes regulating lung injury in mice were screened by RNA sequencing (RNA-seq), and their regulatory effects on inflammation and lung injury were assessed in in vivo and in vitro experiments. Key ResultsThe key regulatory gene KAT2A up-regulated the expression of inflammatory cytokines and induced lung epithelial injury. Chlorogenic acid, a small natural molecule and KAT2A inhibitor, inhibited the inflammatory response and significantly improved the decreased respiratory function caused by lipopolysaccharide administration in mice by inhibiting the expression of KAT2A. Conclusion and ImplicationsTargeted inhibition of KAT2A suppressed the release of inflammatory cytokines and improved respiratory function in this murine model of ALI. Chlorogenic acid, a specific KAT2A-targeting inhibitor, was effective in treating ALI. In conclusion, our results provide a reference for the clinical treatment of ALI and contribute to the development of novel therapeutic drugs for lung injury.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据