Emergency Department, School of Medicine, Nanjing Tongren HospitalSoutheast UniversityJiangning District, Longhu Wenxin garden, No. 99, Lantai street, Nanjing, 211102, Jiangsu, China.
Special Functions Section, The Fourth Sanatorium Area of Hangzhou Special Service Sanatorium Center of Air Force, Nanjing, 210000, Jiangsu, China.
Inflamm Res. 2022 Jun;71(5-6):603-614. doi: 10.1007/s00011-022-01556-4. Epub 2022 Mar 19.
Acute lung injury (ALI) is mostly relevant to acute and severe lung inflammation. We first utilized lipopolysaccharide (LPS) to induce mice for establishing a mouse model of ALI and detected decreased expression of GPR43 in the lung tissue in mice with ALI. Mice expressing increased GPR43 showed improvement in lung injury compared to LPS-treated mice. Additionally, ALI mice transfected with lenti-GPR43 significantly decreased the mRNA levels of TNF-α, IL-1β, IL-6, MPO, COX2 and iNOS, and apoptosis levels in the lungs, as well as the phosphorylation levels of JNK and ELK1 compared to LPS-treated mice with lenti-vector infection. Subsequently, we employed LPS to induce alveolar type ii epithelial cells and observed that Ov-GPR43 infection markedly reduced the expression levels of inflammatory factors and apoptosis levels, while exposure of cells to anisomycin was also effective in blunting the effects of Ov-GPR43 on these processes. Taken together, these results demonstrate a role of GPR43 in mediating lung injury through JNK/ELK1 and imply the therapeutic potential of targeting GPR43 against ALI.
急性肺损伤（ALI）主要与急性和严重的肺部炎症有关。我们首先利用脂多糖（LPS）诱导小鼠建立 ALI 小鼠模型，并检测到 ALI 小鼠肺组织中 GPR43 的表达降低。与 LPS 处理的小鼠相比，表达增加的 GPR43 的小鼠的肺损伤得到改善。此外，与 LPS 处理的感染 lentivector 的 ALI 小鼠相比，用 lenti-GPR43 转染的 ALI 小鼠肺中 TNF-α、IL-1β、IL-6、MPO、COX2 和 iNOS 的 mRNA 水平以及细胞凋亡水平以及 JNK 和 ELK1 的磷酸化水平均显著降低。随后，我们利用 LPS 诱导肺泡型 II 上皮细胞，观察到 Ov-GPR43 感染显著降低了炎症因子的表达水平和细胞凋亡水平，而细胞暴露于 anisomycin 也能有效阻断 Ov-GPR43 对这些过程的影响。综上所述，这些结果表明 GPR43 通过 JNK/ELK1 介导肺损伤，并提示靶向 GPR43 治疗 ALI 的治疗潜力。
