Citrus alkaline extracts improve LPS-induced pulmonary fibrosis via epithelial mesenchymal transition signals.
Citrus alkaline extracts improve LPS-induced pulmonary fibrosis via epithelial mesenchymal transition signals.
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DOI：
10.1186/s13020-023-00766-0
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发表时间：
2023-05-29
期刊：
影响因子：
4.9
通讯作者：
中科院分区：
文献类型：
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作者：
急性呼吸窘迫综合征（ARDS）是一种严重威胁生命的临床危重症。ARDS相关性肺纤维化是ARDS的常见并发症。早期肺纤维化的发生提示多器官功能衰竭的发生率和死亡率较高。本研究建立了LPS诱导的小鼠ARDS相关肺纤维化模型。并对柑桔碱提取物（CAE）的体内外抗肺纤维化作用及其分子机制进行了初步探讨。本研究建立了小鼠肺纤维化模型和肺上皮细胞损伤模型。H&E、Masson和天狼星红染色用于评估肺组织损伤。免疫组化和Western blotting分析蛋白表达。通过免疫共沉淀法观察蛋白质-蛋白质相互作用。通过RNA-seq检查CAE对信号传导途径的系统性影响。通过H&E、Masson和天狼星红染色，令人信服地表明治疗性施用CAE减轻肺损伤和纤维化，而预处理施用CAE显示出微弱的改善。体外实验表明，CAE对上皮间质转化（EMT）的重要指标E-cadherin和N-cadherin具有双重调节作用。CAE主要通过Wnt/β-catenin、Stat 3/6和COX 2/PGE 2信号通路逆转TGF-β1诱导的EMT。通过RNA-Seq，我们发现了CAE发挥其治疗作用的重要机制。网络药理学分析揭示了CAE在EMT中的核心潜在靶点。本研究为CAE抗肺纤维化提供了新的治疗作用，并为CAE治疗LPS诱导的肺纤维化提供了可能的机制。在线版本包含补充材料，可通过10.1186/s13020-023-00766-0获得。
Acute respiratory distress syndrome (ARDS) is a serious life threatening clinical critical illness. ARDS-related pulmonary fibrosis is a common complication of ARDS. The occurrence of early pulmonary fibrosis indicates a higher incidence and mortality of multiple organ failure. LPS-induced ARDS-related pulmonary fibrosis model in mice was established in this study. And we have explored the anti-pulmonary fibrosis effects and molecular mechanisms of the Citrus Alkaline Extracts (CAE) in vivo and in vitro. Pulmonary fibrosis mouse model and lung epithelial cell injury model were established in this study. H&E, Masson and Sirius Red staining were used to estimate lung tissue damage. Immunohistochemistry and western blotting were used to analyze proteins expression. Protein-protein interaction was observed by Co-Immunoprecipitation. Systemic impact of CAE on signaling pathway was examined by RNA-seq. Through H&E, Masson and Sirius Red staining, it was convincingly indicated that therapeutic administration of CAE alleviated lung injury and fibrosis, while pretreated administration of CAE showed weak improvement. In vitro experiments showed that CAE had dual regulation to E-cadherin and N-cadherin, the important indicators of epithelial-mesenchymal transition (EMT). And it was further demonstrated that CAE reversed TGF-β1-induced EMT mainly through Wnt/β-catenin, Stat3/6 and COX2/PGE2 signals. Through RNA-Seq, we discovered important mechanisms by which CAE exerts its therapeutic effect. And network pharmacology analysis demonstrated core potential targets of CAE in EMT. Thus, this study provides new therapeutic effects of CAE in anti-fibrosis, and offers potential mechanisms for CAE in LPS-induced pulmonary fibrosis. The online version contains supplementary material available at 10.1186/s13020-023-00766-0.
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影响因子：
5.8
作者：
Suzuki T;Tada Y;Gladson S;Nishimura R;Shimomura I;Karasawa S;Tatsumi K;West J
通讯作者：
West J
影响因子：
2.9
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5.2
作者：
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影响因子：
3.7
作者：
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通讯作者：
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影响因子：
11.1
作者：
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