{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:59:06Z","timestamp":1788339546159,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700951"],"award-info":[{"award-number":["81700951"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771095"],"award-info":[{"award-number":["81771095"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81803186"],"award-info":[{"award-number":["81803186"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To investigate the synergetic regulatory effect of miR\u201022 on HIF\u20101\u03b1 and NLRP3, subsequently regulating the production of the NLRP3\/CASP1 inflammasome pathway\u2010mediated proinflammatory cytokines IL\u20101\u03b2 and IL\u201018 in human dental pulp fibroblasts (HDPFs) during the progression of pulpitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p>Fluorescence in situ hybridization (FISH) and immunofluorescence (IF) were performed to determine the localization of miR\u201022\u20103p, NLRP3 and HIF\u20101\u03b1 in human dental pulp tissues (HDPTs). The miR\u201022 mimics and inhibitor or plasmid of NLRP3 or HIF\u20101\u03b1 were used to upregulate or downregulate miR\u201022 or NLRP3 or HIF\u20101\u03b1 in HDPFs, respectively. Computational prediction via TargetScan 5.1 and a luciferase reporter assay were conducted to confirm target association. The mRNA and protein expression of HIF\u20101\u03b1, NLRP3, caspase\u20101, IL\u20101\u03b2 and IL\u201018 were determined by qRT\u2010PCR and western blotting, respectively. The release of IL\u20101\u03b2 and IL\u201018 was analysed by ELISA. The significance of the differences between the experimental and control groups was determined by one\u2010way analysis of variance, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05 indicated statistical significance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A decrease in miR\u201022 and an increase in HIF\u20101\u03b1 and NLRP3 in HDPTs occurred during the transformation of reversible pulpitis into irreversible pulpitis compared with that in the healthy pulp tissues (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05). In the normal HDPTs, miR\u201022\u20103p was extensively expressed in dental pulp cells. HIF\u20101\u03b1 and NLRP3 were mainly expressed in the odontoblasts and vascular endothelial cells. Whereas in the inflamed HDPTs, the odontoblast layers were disrupted. HDPFs were positive for miR\u201022\u20103p, HIF\u20101\u03b1 and NLRP3. Computational prediction via TargetScan 5.1 and luciferase reporter assays confirmed that both NLRP3 and HIF\u20101\u03b1 were direct targets of miR\u201022 in HDPFs. The miR\u201022 inhibitor further promoted the activation of NLRP3\/CASP1 inflammasome pathway induced by ATP plus LPS and hypoxia (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05). In contrast, the miR\u201022 mimic significantly inhibited the NLRP3\/CASP1 inflammasome pathway activation induced by ATP plus LPS and hypoxia (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MiR\u201022, as a synergetic negative regulator, is involved in controlling the secretion of proinflammatory cytokines mediated by the NLRP3\/CASP1 inflammasome pathway by targeting NLRP3 and HIF\u20101\u03b1. These results provide a novel function and mechanism of miR\u201022\u2010HIF\u20101\u03b1\u2010NLRP3 signalling in the control of proinflammatory cytokine secretion, thus indicating a potential therapeutic strategy for future endodontic treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iej.13814","type":"journal-article","created":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T06:30:56Z","timestamp":1660804256000},"page":"1225-1240","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["<scp>MicroRNA<\/scp>\u201022 suppresses <scp>NLRP3<\/scp>\/<scp>CASP1<\/scp> inflammasome pathway\u2010mediated proinflammatory cytokine production by targeting the <scp>HIF<\/scp>\u20101\u03b1 and <scp>NLRP3<\/scp> in human dental pulp 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