Periostin aggravates NLRP3 inflammasome-mediated pyroptosis in myocardial ischemia-reperfusion injury.

Abstract Pyroptosis is a form of caspase-1-induced programmed cell death. This study aimed to investigate the effect of periostin (postn) on pyroptosis in myocardial ischemia-reperfusion injury (MIRI). To this end, the differentially expressed genes were obtained from the GSE4105 dataset using the “GEO2R” online tool. Protein-protein interaction networks were constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database, and Module and Go analysis were conducted using the Cytoscape 3.6 plugs-in MCODE and BINGO, respectively. The analysis showed that postn was a critical gene in the most significant module. Experimental results, including triphenyltetrazolium chloride staining, pathological analysis, TUNEL staining, western blotting, and RT-qPCR assays, showed that MIRI induced caspase-1-mediated pyroptosis by activating the NLRP3 inflammasome. Postn was significantly upregulated in the heart tissues of MIRI rats and in H9C2 cells following hypoxia/reoxygenation (H/R) treatment. In addition, knockdown of postn suppressed the caspase-1-mediated pyroptosis and H/R-mediated NLRP3 inflammasome activation, as evidenced by flow cytometry, CCK8, RT-qPCR, western blotting, and ELISA assays. In contrast, overexpression of postn promoted NLRP3 inflammasome-mediated pyroptosis of H/R-treated H9C2 cells. According to the results of rescue experiments, a caspase-1 inhibitor reduced the increase in NLRP3 inflammasome-mediated pyroptosis induced by overexpression of postn, and the pyroptosis-promoting function of postn overexpression in H/R treated H9C2 cells was reversed by inhibition of NLRP3. In conclusion, postn overexpression promoted the caspase-1-mediated pyroptosis during MIRI by activating the NLRP3.