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

Abstract 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.