Exosomal lncRNA-p21 derived from mesenchymal stem cells protects epithelial cells during LPS-induced acute lung injury by sponging miR-181.

Abstract

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.