Deletion of G protein-coupled receptor 116 enhances neutrophil function and aggravates lung injury in mice.
Deletion of G protein-coupled receptor 116 enhances neutrophil function and aggravates lung injury in mice.
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G蛋白偶联受体116缺失增强小鼠中性粒细胞功能并加重肺损伤
DOI：
10.1016/j.gendis.2022.08.017
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发表时间：
2023-07
期刊：
影响因子：
6.8
通讯作者：
Bian, Jinjun
中科院分区：
文献类型：
--
作者：
Wang, Ting;Wang, Ying;Xiang, Qian;Lin, Shengwei;Jin, Peipei;Wang, Jun;Li, Na;Wang, Jiafeng;Bian, Jinjun
急性肺损伤（ALI）每年在全球范围内折磨着超过300万人。最终可发展为急性呼吸窘迫综合征（ARDS），死亡率高达40%。迄今为止，由于临床方法的疗效不佳和缺乏经证实的药理学靶点，ALI的治疗一直不足。1G蛋白偶联受体（1G protein-coupled receptors，GPCRs）广泛参与人体生理和病理生理的调节，是现代医学研究的重要靶点。其中，表达于肺泡上皮细胞和免疫细胞的Gpr116被报道在维持肺泡内环境稳定和抑制炎症方面发挥关键作用。2然而，其在中性粒细胞功能和ALI的调节中的作用仍有待阐明。本研究采用脂多糖（lipopolysaccharide，LPS）诱导的小鼠肺损伤模型，观察Gpr116对中性粒细胞功能的抑制作用。在体外用佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）（100 ng/mL）刺激从对照和髓样细胞特异性Gpr116敲除小鼠的骨髓中分离的中性粒细胞。补充材料中提供了更多详细信息。
Acute lung injury (ALI) globally afflicts over 3 million individuals every year. It can eventually develop into acute respiratory distress syndrome (ARDS) with a high mortality of up to 40%. To date, ALI has been undertreated in terms of the feeble efficacy of clinical approaches and the lack of proven pharmacological targets. 1 G protein-coupled receptors (GPCRs), the promising targets of modern medicine, participate intensively in the regulation of human physiology and pathophysiology. Among them, Gpr116, which is expressed in alveolar epithelial cells and immune cells, has been reported to play a key role in maintaining alveolar homeostasis and inhibiting inflammation. 2 However, its role in the regulation of neutrophil function and ALI remains to be elucidated. In this study, we demonstrated the inhibitory role of Gpr116 on neutrophil function, which contributes to nonspecific lung injury in mice induced by lipopolysaccharide (LPS).In brief, LPS was intratracheally injected at a dose of 10 mg/kg in mice to induce ALI in vivo. Neutrophils isolated from the bone marrow of control and myeloid cell-specific Gpr116 knockout mice were stimulated with phorbol 12-myristate 13-acetate (PMA)(100 ng/mL) in vitro. More details are available in the Supplementary materials.
影响因子：
7.3
作者：
Shi, Yue;Liu, Tingting;Chen, Peijie
通讯作者：
Chen, Peijie
影响因子：
8
作者：
Lefrancais, Emma;Mallavia, Benat;Looney, Mark R.
通讯作者：
Looney, Mark R.
影响因子：
5.8
作者：
Kubo, Fumimasa;Ariestanti, Donna Maretta;Nakamura, Nobuhiro
通讯作者：
Nakamura, Nobuhiro