Yang Jing, Huang Qikun, Liao Peiyuan, Zhang Pingli, Sun Shijing, Xu Qianwen
Department of Pediatric, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266035, Shandong, China.
Department of Pediatric, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266035, Shandong, China.
Transpl Immunol. 2023 Feb;76:101681. doi: 10.1016/j.trim.2022.101681. Epub 2022 Aug 1.
Sepsis is recognized as an inflammation-related syndrome in response to invading pathogens. Many patients suffer from sepsis including transplant recipients. Lipopolysaccharide (LPS) is known to trigger sepsis-related organ dysfunction. This study expounded on the possible effect of microRNA (miR)-338-3p in sepsis-induced acute lung injury (ALI). Firstly, human bronchial epithelial cell line 16HBE received LPS treatment to establish the cell models of sepsis-induced ALI. The expression patterns of miR-338-3p, long non-coding RNA OPA-interacting protein 5 antisense transcript 1 (lncRNA OIP5-AS1), and activating transcription factor 4 (ATF4) in 16HBE cells were examined. Afterwards, 16HBE cell viability, the apoptosis rate, and the levels of inflammation and lactate dehydrogenase (LDH) were determined to assess the degree of cell injury. We disclosed that LPS treatment triggered 16HBE cell injury, downregulated miR-338-3p, and upregulated OIP5-AS1 and ATF4. miR-338-3p overexpression repressed LPS-induced 16HBE cell injury. miR-338-3p diminished OIP5-AS1 stability via binding to OIP5-AS1 and downregulated OIP5-AS1 expression and OIP5-AS1 can enhance ATF4 mRNA stability and upregulate ATF4 mRNA level. The rescue experiments showed that ATF4 overexpression aggravated LPS-induced 16HBE cell injury. Overall, miR-338-3p overexpression decreased OIP5-AS1 expression and stability and further downregulated ATF4 mRNA level, thereby mitigating LPS-induced 16HBE cell injury.
脓毒症被认为是一种针对入侵病原体的炎症相关综合征。许多患者患有脓毒症，包括移植受者。已知脂多糖（LPS）会引发脓毒症相关的器官功能障碍。本研究阐述了微小RNA（miR）-338-3p在脓毒症诱导的急性肺损伤（ALI）中的可能作用。首先，人支气管上皮细胞系16HBE接受LPS处理以建立脓毒症诱导的ALI细胞模型。检测16HBE细胞中miR-338-3p、长链非编码RNA OPA相互作用蛋白5反义转录本1（lncRNA OIP5-AS1）和激活转录因子4（ATF4）的表达模式。随后，测定16HBE细胞活力、凋亡率以及炎症和乳酸脱氢酶（LDH）水平，以评估细胞损伤程度。我们发现LPS处理引发了16HBE细胞损伤，下调了miR-338-3p，并上调了OIP5-AS1和ATF4。miR-338-3p过表达抑制了LPS诱导的16HBE细胞损伤。miR-338-3p通过与OIP5-AS1结合降低了OIP5-AS1的稳定性，下调了OIP5-AS1的表达，并且OIP5-AS1可以增强ATF4 mRNA的稳定性并上调ATF4 mRNA水平。拯救实验表明，ATF4过表达加重了LPS诱导的16HBE细胞损伤。总体而言，miR-338-3p过表达降低了OIP5-AS1的表达和稳定性，并进一步下调了ATF4 mRNA水平，从而减轻了LPS诱导的16HBE细胞损伤。
