Rapamycin inhibits LOC102553434-mediated pyroptosis to improve lung injury induced by limb ischemia-reperfusion

The study was aimed to explore whether pyroptosis was involved in the process of rapamycin alleviating lung injury induced by limb ischemia/reperfusion and investigate the molecular mechanisms involved in this process. The histopathology of lung injury induced by I/R was confirmed by hematoxylin-eosin (HE) staining, and malondialdehyde (MDA), superoxide dismutase (SOD), and the expression of pyroptosis related molecules were detected. RNA sequencing were used to mine key lncRNAs. The model of LPS-induced L2 cell damage was also used to explore the effect and mechanism of rapamycin on lncRNA. Rapamycin treatment alleviated I/R - induced lung histopathological injury, and increased the concentration of MDA while decreased activity of SOD and expression of NLRP3, Caspase-1, IL, and L-18 in rat. A total of 63 differentially expressed lncRNAs (DElncRNAs) were identified from IR+Rap group compared with IR group, and these DElncRNAs were mainly involved in cell adhersion molecules (CAMs) and endocytosis pathway. LOC102553434 and its target gene MMP9 were most significantly up-regulated in I/R-injured rat. In vitro experiments showed that LPS induction caused a significant increase in LOC102553434, MMP9, IL, and L-18 in L2 cells, but rapamycin treatment significantly reversed the effects. After interfering the expression of LOC102553434 in the LPS-injured cells pretreated with rapamycin, cell proliferation significantly increased, and the expression of MMP, NLRP3 and capase-1 were significantly decreased. Rapamycin protects the lung from limb injury by regulating LOC102553434 expression and inhibiting pyroptosis pathway. LOC102553434 plays a role in promoting pyroptosis and thus provides a target for clinical treatment of induced lung injury.