GATA1-activated lncRNA OIP5-AS1 and GAS5 promote pyroptosis to exacerbate asthma through regulating miR-136-5p/LIFR axis

Pyroptosis plays a pivotal role in airway epithelial inflammation during the progression of asthma. This study aimed to explore the influence and mechanisms of opa-interacting protein 5 antisense RNA1 (OIP5-AS1) and growth arrest-specific transcript 5 (GAS5) on Pyroptosis in asthmatic models. Pyroptosis was induced in Dermatophagoides pteronyssinus 1 (Der p1)-exposed 16HBE cells and ovalbumin (OVA)-challenged rats. Subsequently, Pyroptosis and its related molecular mechanisms were investigated. Our results indicated that GATA1, OIP5-AS1, GAS5, and LIFR were upregulated, while miR-136-5p was downregulated in the patients and experimental models of asthma. OIP5-AS1/GAS5 knockdown repressed NLRP3 inflammasome-mediated Pyroptosis in 16HBE cells. Mechanistically, OIP5-AS1/GAS5 sponged miR-136-5p to enhance LIFR expression and subsequently activated NF-κB pathway. OIP5-AS1, GAS5, or LIFR-mediated induction of Pyroptosis was abrogated by miR-136-5p mimics or NF-κB inhibitors (BAY11-7082). Finally, GATA1 transcriptionally activated OIP5-AS1/GAS5 to trigger Pyroptosis, thereby driving asthma progression in vivo and in vitro. In conclusion, OIP5-AS1/GAS5 transcriptionally activated by GATA1 promoted NLRP3 inflammasome-mediated Pyroptosis via the modulation of miR-136-5p/LIFR/NF-κB axis and consequently resulted in airway inflammation in asthma. Our results may provide novel therapeutic strategies for asthma.

GAS5; LIFR; OIP5‐AS1; asthma; miR‐136‐5p; pyroptosis.