Periostin aggravates NLRP3 inflammasome-mediated pyroptosis in myocardial ischemia-reperfusion injury |
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| Institution: | 1. Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran;2. Stem Cell and Regenerative Medicine (SCARM), Tabriz University of Medical Sciences, Tabriz, Iran;3. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;4. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;5. Professor of Anesthesiology, Al-Zahra Hospital, Tabriz University of Medical Sciences, Tabriz, Iran;6. Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;1. Department of Otolaryngology–Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China;3. Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, China;2. Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China;4. Upper Airways Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium;1. Department of Anesthesiology, Second Affiliated Hospital of Nanchang University, 330006, Nanchang, Jiangxi Province, P.R. China;2. Queen Mary School, Nanchang University, 330006, Nanchang, Jiangxi Province, P.R. China;1. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, 610041, PR China;2. Department of Neurology, Chongzhou People’s Hospital, Chengdu, 611230, PR China;1. Department of Cardiology, The Sixth Medical Center, Chinese PLA General Hospital, Beijing, 100700, China;2. Department of Cardiology, Airforce Medical Center, PLA, Beijing, 100142, China;3. Department of General Surgery, Airforce Medical Center, PLA, Beijing, 100142, China |
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| 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. |
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| Keywords: | Postn Caspase-1 Pyroptosis Ischemia-reperfusion NLRP3 MIRI |
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