Peethambaran Divya, Puthusseri Bijesh, Kumar Gyanendra, Janani Rajasekar, Giridhar Parvatam, Baskaran Vallikannan
Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysore, 570020, Karnataka, India.
Department of Plant Cell Biotechnology, CSIR-Central Food Technological Research Institute, Mysore, 570020, Karnataka, India.
Inflammation. 2023 Jun;46(3):941-962. doi: 10.1007/s10753-023-01782-w. Epub 2023 Jan 26.
Exacerbated inflammation and apoptosis are considered upstream events associated with acute lung injury (ALI). microRNAs are critical regulators of genes responsible for inflammation and apoptosis and are considered potential therapeutic targets for ameliorating ALI. This study was undertaken to uncover the role of miR-7-5p in LPS-induced lung injury. A LPS-induced inflammation model was established using BEAS-2B cells and C57BL/6 mice. Bioinformatics analysis and the luciferase reporter assay confirmed that Raf-1 is a target of miR-7-5p and that its expression was inversely correlated with expression of proinflammatory markers and miR-7-5p, whereas miR-7-5p inhibition in vitro led to subsequent restoration of Raf-1 expression and prevention of apoptosis. Intranasal (i.n.) administration of antagomir using the C57BL/6 mouse model further confirmed that miR-7-5p inhibition suppresses LPS-induced inflammation and apoptosis via modulating the miR-7-5p/Raf-1 axis. Our findings indicate that blocking miR-7-5p expression by antagomir protects mice from LPS-induced lung injury by suppressing inflammation and activation of mitochondria-mediated survival signalling. In conclusion, our findings demonstrate a previously unknown pathophysiological role of miR-7-5p in the progression of ALI, and targeted i.n. administration of miR-7-5p antagomir could aid in the development of potential therapeutic strategies against lung injury.
炎症加剧和细胞凋亡被认为是与急性肺损伤（ALI）相关的上游事件。微小RNA是负责炎症和细胞凋亡的基因的关键调节因子，被认为是改善ALI的潜在治疗靶点。本研究旨在揭示miR-7-5p在脂多糖（LPS）诱导的肺损伤中的作用。使用BEAS-2B细胞和C57BL/6小鼠建立了LPS诱导的炎症模型。生物信息学分析和荧光素酶报告基因检测证实，Raf-1是miR-7-5p的靶标，其表达与促炎标志物和miR-7-5p的表达呈负相关，而体外抑制miR-7-5p可导致Raf-1表达恢复并预防细胞凋亡。使用C57BL/6小鼠模型经鼻内（i.n.）给予抗miR进一步证实，抑制miR-7-5p可通过调节miR-7-5p/Raf-1轴抑制LPS诱导的炎症和细胞凋亡。我们的研究结果表明，通过抗miR阻断miR-7-5p表达可通过抑制炎症和线粒体介导的生存信号激活来保护小鼠免受LPS诱导的肺损伤。总之，我们的研究结果证明了miR-7-5p在ALI进展中以前未知的病理生理作用，经鼻内给予miR-7-5p抗miR可能有助于开发针对肺损伤的潜在治疗策略。
