Emergency Department, The First Hospital of China Medical University, Shenyang 110001, China.
Acta Biochim Biophys Sin (Shanghai). 2021 May 21;53(6):748-757. doi: 10.1093/abbs/gmab043.
Long noncoding RNAs (lncRNAs) act as essential regulators of various diseases. However, the functions of lncRNAs in sepsis-induced acute lung injury (SALI) remain unclear. Here, we found that lipopolysaccharide could upregulate lncRNA-p21 expression in mesenchymal stem cells (MSCs) in a time- and dose-dependent manner and that lncRNA-p21 was packaged into exosomes. Furthermore, we demonstrated that treatment with exosomal lncRNA-p21 could increase the expression of sirtuin 1 (SIRT1) to protect MLE-12 cells from apoptosis during sepsis. Moreover, we identified SIRT1 as a direct target of miR-181 and found that the level of SIRT1 was negatively correlated with the level of miR-181. The luciferase reporter assay also confirmed the negative correlation between the levels of miR-181 and lncRNA-p21. Our results showed that the lncRNA-p21-induced downregulation of miR-181 might suppress epithelial cell apoptosis and alleviate lung tissue injury by upregulating SIRT1 expression, suggesting the potential therapeutic effects of lncRNA-p21 on SALI. In conclusion, we found that the novel lncRNA-p21/miR-181/SIRT1 pathway may play an important role in the progression of SALI, and MSC-derived exosomes may be a new therapeutic strategy for this disease.
长链非编码 RNA（lncRNA）作为各种疾病的重要调节剂。然而，lncRNA 在脓毒症诱导的急性肺损伤（SALI）中的作用尚不清楚。在这里，我们发现脂多糖可以时间和剂量依赖性地上调间充质干细胞（MSCs）中的 lncRNA-p21 表达，并且 lncRNA-p21 被包装到外泌体中。此外，我们证明了外泌体 lncRNA-p21 的处理可以增加沉默调节蛋白 1（SIRT1）的表达，以保护 MLE-12 细胞免受脓毒症期间的凋亡。此外，我们确定 SIRT1 是 miR-181 的直接靶标，并发现 SIRT1 的水平与 miR-181 的水平呈负相关。荧光素酶报告基因检测也证实了 miR-181 和 lncRNA-p21 水平之间的负相关关系。我们的结果表明，lncRNA-p21 诱导的 miR-181 下调可能通过上调 SIRT1 表达抑制上皮细胞凋亡并减轻肺组织损伤，表明 lncRNA-p21 对 SALI 具有潜在的治疗作用。总之，我们发现新型 lncRNA-p21/miR-181/SIRT1 通路可能在 SALI 的进展中起重要作用，而 MSC 衍生的外泌体可能是该疾病的一种新的治疗策略。
