LncRNA ZFAS1 plays a role in regulating the inflammatory responses in sepsis-induced acute lung injury via mediating miR-193a-3p

Objective: To explore the role of lncRNA ZFAS1-mediated miR-193a-3p in the regulation of inflammatory responses in rats with sepsis-induced acute lung injury (ALI). Methods: Sepsis-induced ALI models were constructed by LPS induction and then injected with ZFAS1 overexpression plasmid. Thereafter, lung injury score and the W/D weight ratio were calculated. Besides, bronchoalveolar lavage fluid (BALF) was isolated from rats to perform the cell count and protein quantification, while qRT-PCR and ELISA were performed to detect the inflammatory cytokines expressions. In vitro, NR8383 cells were transfected and then treated with LPS, followed by the measurement of inflammatory cytokines, cell viability and cell apoptosis. Results: In comparison with the Control group, rats in the LPS group presented sharp increases in the W/D weight ratio and injury score of lung, total protein concentration and the count of neutrophils and macrophages in BALF. Besides, rats in LPS group also resulted in a decrease in ZFAS1 expression and increase in miR-193a-3p expression in lung tissues, with the increased pro-inflammatory cytokines. Dual luciferase reporter gene assay confirmed a target relation between miR-193a-3p and ZFAS1. As compared to the Blank group, NR8383 cells in the LPS group had up-regulated pro-inflammatory cytokines with declined cell viability and elevated cell apoptosis; and meanwhile, ZFAS1 and Bcl-2 were decreased but miR-193a-3p and Bax were increased. Overexpression of ZFAS1 could significantly improve LPS-induced ALI in vivo and in vitro with reduced levels of proinflammatory cytokines. Conclusion: Overexpression of ZFAS1, possibly via targeting the expression of miR-193a-3p, could inhibit the apoptosis and ameliorate the inflammatory responses of ALI in sepsis.

Automated summary

The overexpression of ZFAS1 significantly improved the inflammatory responses in sepsis-induced ALI rats, possibly by inhibiting apoptosis and promoting levels of proinflammatory cytokines.