{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T16:57:06Z","timestamp":1787590626073,"version":"build-2736575974"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T00:00:00Z","timestamp":1608681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Pulpitis is a frequent bacterially driven inflammation featured with the local accumulation of inflammatory products in human dental pulps. A GEO dataset GSE16134 comprising data of inflamed dental pulp tissues was used for bioinformatics analyses. A protein-protein interaction (PPI) analysis suggested that chemokine receptor 4 (CXCR4) owned a high correlation with platelet endothelial cell adhesion molecule-1 (PECAM1). A rat model with pulpitis was established, and lipopolysaccharide (LPS)-induced human dental pulp fibroblasts (HDPFs) were used for <jats:italic>in vitro<\/jats:italic> experiments. Then, high expression of PECAM1 and CXCR4 was validated in the inflamed dental pulp tissues in rats and in LPS-induced HDPFs. Either downregulation of PECAM1 or CXCR4 suppressed inflammatory cell infiltration in inflamed tissues as well as the inflammation and apoptosis of HDPFs. A transcription factor myocyte-enhancer factor 2 (MEF2C) was predicted and validated as a positive regulator of either PECAM1 or CXCR4, which activated the NF-\u03baB signaling pathway and promoted pulpitis progression. To sum up, this study suggested that MEF2C transcriptionally activates PECAM1 and CXCR4 to activate the B-cell and NF-\u03baB signaling pathways, leading to inflammatory cell infiltration and pulpitis progression.<\/jats:p>","DOI":"10.3389\/fcell.2020.593653","type":"journal-article","created":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T08:27:03Z","timestamp":1608712023000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["PECAM1 Combines With CXCR4 to Trigger Inflammatory Cell Infiltration and Pulpitis Progression Through Activating the NF-\u03baB Signaling Pathway"],"prefix":"10.3389","volume":"8","author":[{"given":"Yonghong","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songbo","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD004969.pub5","article-title":"Antibiotic use for irreversible pulpitis.","volume":"5","author":"Agnihotry","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.joen.2016.10.020","article-title":"ASH1L suppresses matrix metalloproteinase through mitogen-activated protein kinase signaling pathway in pulpitis.","volume":"43","author":"Bei","year":"2017","journal-title":"J. Endod."},{"key":"B3","doi-asserted-by":"publisher","first-page":"23315","DOI":"10.1002\/jcp.28899","article-title":"MiR-199a-3p inhibition facilitates cardiomyocyte differentiation of embryonic stem cell through promotion of MEF2C.","volume":"234","author":"Chen","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"7543","DOI":"10.26355\/eurrev_201811_16296","article-title":"CD31 induces inflammatory response by promoting hepatic inflammatory response and cell apoptosis.","volume":"22","author":"Cheng","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.yexmp.2009.09.013","article-title":"Blocking platelet\/endothelial cell adhesion molecule 1 (PECAM) inhibits disease progression and prevents joint erosion in established collagen antibody-induced arthritis.","volume":"88","author":"Dasgupta","year":"2010","journal-title":"Exp. Mol. Pathol."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/eci.12949","article-title":"CXCR4, the master regulator of neutrophil trafficking in homeostasis and disease.","author":"De Filippo","year":"2018","journal-title":"Eur. J. Clin. Invest."},{"key":"B7","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1111\/jop.12926","article-title":"Astragaloside IV attenuates inflammatory injury and promotes odontoblastic differentiation in lipopolysaccharide-stimulated MDPC-23 cells and rat pulpitis.","volume":"48","author":"Ding","year":"2019","journal-title":"J. Oral Pathol. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1080\/21655979.2019.1621135","article-title":"5-Aza-2\u2019-deoxycytidine enhances lipopolysaccharide-induced inflammatory cytokine expression in human dental pulp cells by regulating TRAF6 methylation.","volume":"10","author":"Feng","year":"2019","journal-title":"Bioengineered"},{"key":"B9","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/gene.2016.14","article-title":"Gene expression profile of pulpitis.","volume":"17","author":"Galicia","year":"2016","journal-title":"Genes Immun."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1016\/j.joen.2010.05.011","article-title":"Regulation of the stromal cell-derived factor-1alpha-CXCR4 axis in human dental pulp cells.","volume":"36","author":"Gong","year":"2010","journal-title":"J. Endod."},{"key":"B11","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1177\/0022034515612022","article-title":"Conditional TNF-alpha overexpression in the tooth and Alveolar bone results in painful pulpitis and osteitis.","volume":"95","author":"Hall","year":"2016","journal-title":"J. Dent. Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1038\/386296a0","article-title":"Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation.","volume":"386","author":"Han","year":"1997","journal-title":"Nature"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1161\/ATVBAHA.108.164707","article-title":"Endothelial cell PECAM-1 promotes atherosclerotic lesions in areas of disturbed flow in ApoE-deficient mice.","volume":"28","author":"Harry","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1016\/j.joen.2008.07.023","article-title":"The expression of stromal cell-derived factor 1 (SDF-1) in inflamed human dental pulp.","volume":"34","author":"Jiang","year":"2008","journal-title":"J. Endod."},{"key":"B15","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1007\/s00223-013-9824-5","article-title":"A ChIP-seq-defined genome-wide map of MEF2C binding reveals inflammatory pathways associated with its role in bone density determination.","volume":"94","author":"Johnson","year":"2014","journal-title":"Calcif. Tissue Int."},{"key":"B16","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1111\/iej.12147","article-title":"Involvement of SDF-1 and monocyte chemoattractant protein-1 in hydrogen peroxide-induced extracellular matrix degradation in human dental pulp cells.","volume":"47","author":"Kim","year":"2014","journal-title":"Int. Endod. J."},{"key":"B17","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1007\/s12149-018-1290-8","article-title":"CXCR4-directed theranostics in oncology and inflammation.","volume":"32","author":"Kircher","year":"2018","journal-title":"Ann. Nucl. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1002\/JPER.18-0604","article-title":"Severe periodontitis may influence cementum and dental pulp through inflammation, oxidative stress, and apoptosis.","volume":"90","author":"Li","year":"2019","journal-title":"J. Periodontol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1139\/bcb-2017-0074","article-title":"The CXCL12-CXCR4 axis promotes migration, invasiveness, and EMT in human papillary thyroid carcinoma B-CPAP cells via NF-kappaB signaling.","volume":"96","author":"Lin","year":"2018","journal-title":"Biochem. Cell Biol."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/2756891","article-title":"OCT4B1 regulates the cellular stress response of human dental pulp cells with inflammation.","volume":"2017","author":"Liu","year":"2017","journal-title":"Biomed. Res. Int."},{"key":"B21","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.archoralbio.2019.05.003","article-title":"Interleukin-17 plays a role in pulp inflammation partly by WNT5A protein induction.","volume":"103","author":"Liu","year":"2019","journal-title":"Arch. Oral Biol."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101266","article-title":"CPUY192018, a potent inhibitor of the Keap1-Nrf2 protein-protein interaction, alleviates renal inflammation in mice by restricting oxidative stress and NF-kappaB activation.","volume":"26","author":"Lu","year":"2019","journal-title":"Redox Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1034\/j.1600-9657.2003.00167.x","article-title":"Influence of age on the behavior of dental pulp of dog teeth after capping with an adhesive system or calcium hydroxide.","volume":"19","author":"Mestrener","year":"2003","journal-title":"Dent. Traumatol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/bs.ircmb.2017.07.007","article-title":"NF-kappaB and the transcriptional control of inflammation.","volume":"335","author":"Mitchell","year":"2018","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"397","DOI":"10.3109\/08830185.2013.818140","article-title":"B-cell receptor signaling inhibitors for treatment of autoimmune inflammatory diseases and B-cell malignancies.","volume":"32","author":"Puri","year":"2013","journal-title":"Int. Rev. Immunol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1093\/jnen\/60.8.798","article-title":"Inhibition of antigen-specific T cell trafficking into the central nervous system via blocking PECAM1\/CD31 molecule.","volume":"60","author":"Qing","year":"2001","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0214337","article-title":"Identification of key regulatory genes connected to NF-kappaB family of proteins in visceral adipose tissues using gene expression and weighted protein interaction network.","volume":"14","author":"Sabir","year":"2019","journal-title":"PLoS One"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10456-017-9583-4","article-title":"Mechanisms of angiogenesis in microbe-regulated inflammatory and neoplastic conditions.","volume":"21","author":"Sajib","year":"2018","journal-title":"Angiogenesis"},{"key":"B29","doi-asserted-by":"publisher","first-page":"247","DOI":"10.15171\/apb.2015.034","article-title":"Cloning and stable expression of cDNA coding for platelet endothelial cell adhesion molecule -1 (PECAM-1, CD31) in NIH-3T3 cell line.","volume":"5","author":"Salehi-Lalemarzi","year":"2015","journal-title":"Adv. Pharm. Bull."},{"key":"B30","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1111\/jcmm.12988","article-title":"Pannexin3 inhibits TNF-alpha-induced inflammatory response by suppressing NF-kappaB signalling pathway in human dental pulp cells.","volume":"21","author":"Song","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1093\/ndt\/gfx317","article-title":"Deletion of connective tissue growth factor ameliorates peritoneal fibrosis by inhibiting angiogenesis and inflammation.","volume":"33","author":"Toda","year":"2018","journal-title":"Nephrol. Dial. Transplant."},{"key":"B32","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1042\/BJ20101220","article-title":"p65 controls NF-kappaB activity by regulating cellular localization of IkappaBbeta.","volume":"434","author":"Valovka","year":"2011","journal-title":"Biochem. J."},{"key":"B33","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1111\/odi.13290","article-title":"Catechins reduce inflammation in lipopolysaccharide-stimulated dental pulp cells by inhibiting activation of the NF-kappaB pathway.","volume":"26","author":"Wang","year":"2020","journal-title":"Oral Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.yexcr.2018.02.008","article-title":"Artemin regulates CXCR4 expression to induce migration and invasion in pancreatic cancer cells through activation of NF-kappaB signaling.","volume":"365","author":"Wang","year":"2018","journal-title":"Exp. Cell Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1089\/dna.2008.0817","article-title":"Platelet-endothelial cell adhesion molecule-1 gene polymorphism and its soluble level are associated with ischemic stroke.","volume":"28","author":"Wei","year":"2009","journal-title":"DNA Cell Biol."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2020.593653\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T08:27:05Z","timestamp":1608712025000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2020.593653\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,23]]},"references-count":35,"alternative-id":["10.3389\/fcell.2020.593653"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2020.593653","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,23]]},"article-number":"593653"}}