Department of Respiratory and Critical Care Medicine, Tianjin Chest Hospital, Tianjin, China.
Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Nankai University, Tianjin, China.
Immunopharmacol Immunotoxicol. 2022 Feb;44(1):58-66. doi: 10.1080/08923973.2021.2002890. Epub 2021 Nov 30.
Acute lung injury (ALI) and resultant acute respiratory distress syndrome (ARDS) are detrimental inflammatory disease associated with high rates of morbidity and mortality due to a lack of effective treatment options. Previous study has demonstrated that an inhibition of geranylgeranyl pyrophosphate synthase large subunit 1 (GGPPS1) show a protective effect against ALI.
In this study, by using connective map (CMAP), we identified catechin as a potential drug to exhibit similar effects to inhibit GGPPS1. Furthermore, we detected the protective effect of catechin on lipopolysaccharide (LPS)-induced ALI and delineated the underlying mechanism.
We found that catechin effectively ameliorated LPS-induced lung inflammation and alleviated the release of cytokines into alveolar space. Notably, miR-182/GGPPS1 signaling pathway was reactivated upon catechin administration, which was essential for the catechin-induced protective effect against ALI.
catechin regulates miR-182/GGPPS1 signaling pathway and efficaciously ameliorates LPS-induced acute lung injury in mice model, which provided a promising therapeutic strategy in ALI and ARDS.
急性肺损伤(ALI)和由此导致的急性呼吸窘迫综合征(ARDS)是一种有害的炎症性疾病,由于缺乏有效的治疗选择,其发病率和死亡率都很高。先前的研究表明,抑制香叶基香叶基焦磷酸合酶大亚基 1(GGPPS1)对 ALI 具有保护作用。
在这项研究中,我们使用连接映射(CMAP)技术,鉴定出表儿茶素是一种具有类似抑制 GGPPS1 作用的潜在药物。此外,我们还检测了表儿茶素对脂多糖(LPS)诱导的 ALI 的保护作用,并阐明了其潜在的机制。
我们发现表儿茶素能有效改善 LPS 诱导的肺炎症,并减轻细胞因子向肺泡空间的释放。值得注意的是,表儿茶素给药后重新激活了 miR-182/GGPPS1 信号通路,这对于表儿茶素诱导的 ALI 保护作用至关重要。
表儿茶素调节 miR-182/GGPPS1 信号通路,有效改善 LPS 诱导的小鼠急性肺损伤,为 ALI 和 ARDS 提供了一种有前途的治疗策略。