Knockdown of lncRNA MEG3 protects against sepsis-induced acute lung injury in mice through miR-93-5p-dependent inhibition of NF-?B signaling pathway

Excessive inflammatory response is a prominent pathogenic hallmark of acute lung injury (ALI). Long noncoding RNA (lncRNA) has been recently reported to play a key role in the pathophysiology of many inflammatory disorders, including ALI. Herein, we attempted to explore the role and underlying mechanism of lncRNA MEG3 in the inflammation in ALI. Firstly, an ALI mouse model was generated via intra-tracheal instillation of lipo-polysaccharide (LPS), and then, the impact of lncRNA MEG3 on lung tissue damage, pulmonary edema, lung microvascular permeability and pulmonary inflammatory response, as well as the ALI mice survival rate was investigated. LncRNA MEG3 was upregulated in lung tissues, and knockdown of lncRNA MEG3 protected mice from LPS-induced ALI, with significantly reduced lung pathological changes, decreased lung wet/dry (W/D) ratio and lung microvascular permeability, attenuated inflammatory response, along with increased ALI mice survival. Moreover, lncRNA MEG3 could sponge miR-93, negatively regulated its expression, and lncRNA MEG3 over -expression liberated the suppression of TLR4 expression caused by miR-93. Further, functional studies demon-strated that the protective effects of lncRNA MEG3 on excessive inflammatory response may be related to miR-93-mediated modulation of TLR4/MyD88/NF-kappa B pathway. Collectively, lncRNA MEG3 inhibition blocked TLR4/ MyD88/NF-kappa B pathway to repress the progression of sepsis-induced lung injury via upregulating miR-93, implying that lncRNA MEG3 might be a viable therapeutic target for ALI.

Automated summary

Long noncoding RNA MEG3 plays a critical role in acute lung injury (ALI) by negatively regulating miR-93 and inhibiting the activation of the TLR4/MyD88/NF-kappa B pathway, leading to reduced inflammation and lung tissue damage.