Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai, 200433, China.
Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, PR China; Northern Translational Medicine Research and Cooperation Center, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, 150081, PR China.
Exp Cell Res. 2023 Sep 1;430(1):113685. doi: 10.1016/j.yexcr.2023.113685. Epub 2023 Jun 16.
Acute lung injury (ALI), a common clinical type of critical illness, is an acute hypoxic respiratory insufficiency caused by the damage of alveolar epithelial cells and capillary endothelial cells. In a previous study, we reported a novel lncRNA, lncRNA PFI, which could protect against pulmonary fibrosis in pulmonary fibroblasts. The present study demonstrated that lncRNA PFI was downregulated in alveolar epithelial cell of mice injury lung tissues, and further investigated the role of lncRNA PFI in regulating inflammation-induced alveolar epithelial cell apoptosis. Overexpression of lncRNA PFI could partially abrogated bleomycin induced type II AECs injured. Subsequently, bioinformatic prediction revealed that lncRNA PFI might directly bind to miR-328-3p, and further AGO-2 RNA binding protein immunoprecipitation (RIP) assay confirmed their binding relationship. Furthermore, miR-328-3p promoted apoptosis in MLE-12 cells by limiting the activation of the Creb1, a protein correlated with cell apoptosis, whereas AMO-328-3p ablated the pro-apoptosis effect of silencing lncRNA PFI in MLE-12 cells. While miR-328-3p could also ablate the function of lncRNA PFI in bleomycin treated human lung epithelial cells. Enhanced expression of lncRNA PFI reversed the LPS-induced lung injury in mice. Overall, these data reveal that lncRNA PFI mitigated acute lung injury through miR-328-3p/Creb1 pathway in alveolar epithelial cells.
急性肺损伤 (ALI) 是一种常见的危重病临床类型,是由肺泡上皮细胞和毛细血管内皮细胞损伤引起的急性低氧性呼吸功能不全。在之前的研究中,我们报道了一种新的长非编码 RNA(lncRNA)lncRNA PFI,它可以防止肺成纤维细胞中的肺纤维化。本研究表明,lncRNA PFI 在损伤肺组织的肺泡上皮细胞中下调,并进一步研究了 lncRNA PFI 调节炎症诱导的肺泡上皮细胞凋亡的作用。lncRNA PFI 的过表达可部分减轻博莱霉素诱导的 II 型 AEC 损伤。随后,生物信息学预测表明,lncRNA PFI 可能直接与 miR-328-3p 结合,并进一步通过 AGO-2 RNA 结合蛋白免疫沉淀 (RIP) 实验证实了它们的结合关系。此外,miR-328-3p 通过限制与细胞凋亡相关的 Creb1 蛋白的激活,促进 MLE-12 细胞凋亡,而 AMO-328-3p 消除了沉默 lncRNA PFI 在 MLE-12 细胞中促凋亡的作用。miR-328-3p 还可以消除 lncRNA PFI 在博莱霉素处理的人肺上皮细胞中的作用。lncRNA PFI 的过表达逆转了 LPS 诱导的小鼠肺损伤。总之,这些数据表明,lncRNA PFI 通过 miR-328-3p/Creb1 通路减轻了肺泡上皮细胞中的急性肺损伤。