PECAM1 Combines With CXCR4 to Trigger Inflammatory Cell Infiltration and Pulpitis Progression Through Activating the NF-κB Signaling Pathway

Abstract

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 in vitro 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-κB 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-κB signaling pathways, leading to inflammatory cell infiltration and pulpitis progression.

Role of Lipopolysaccharide, Derived from Various Bacterial Species, in Pulpitis—A Systematic Review

“…It also triggers increased production of C5a—a chemotactic factor, taking part in recruiting inflammatory cells and pulp cells responsible for regeneration [ 114 ]. LPS-stimulated fibroblasts have increased mRNA and protein expressions of myocyte-enhancer factor 2 (MEF2C), platelet endothelial cell adhesion molecule-1 (PECAM1) and CXCR4 [ 115 ]. PECAM1 expression is positively correlated with B-cell signaling pathways, it also plays a role in angiogenesis [ 115 ].…”

“…LPS-stimulated fibroblasts have increased mRNA and protein expressions of myocyte-enhancer factor 2 (MEF2C), platelet endothelial cell adhesion molecule-1 (PECAM1) and CXCR4 [ 115 ]. PECAM1 expression is positively correlated with B-cell signaling pathways, it also plays a role in angiogenesis [ 115 ]. Binding PECAM1 to CXCR4 may intensify inflammation and apoptosis via NF-kB signaling pathway [ 115 ].…”

“…PECAM1 expression is positively correlated with B-cell signaling pathways, it also plays a role in angiogenesis [ 115 ]. Binding PECAM1 to CXCR4 may intensify inflammation and apoptosis via NF-kB signaling pathway [ 115 ]. LPS upregulates NLRP3 inflammasome and pro-IL-1β expression via TLR4/MyD88/NF-κB pathway [ 116 ].…”

Network pharmacology combined with GEO database identifying the mechanisms and molecular targets of Polygoni Cuspidati Rhizoma on Peri-implants

“…A previous report by Cheng et al 89 suggested that PECAM1 was critical in the inflammatory response and apoptosis of hepatitis liver. Meanwhile, Liu et al found that PECAM1 could interact with CXCR4 in experimental pulpitis in mice, which lead to inflammatory response and increased apoptosis of human pulp fibroblasts by activating the NF-KB signaling pathway 90 . Wu found that PECAM-1 was found to be a negative regulator of monocyte derived osteoclast formation in PECAM-1 knockout mice 91 .…”

Combination of resolvin E1 and lipoxin A4 promotes the resolution of pulpitis by inhibiting NF‐κB activation through upregulating sirtuin 7 in dental pulp fibroblasts

“…The key to sequestrating pro‐inflammatory factors is to inhibit the cascade of inflammatory pathway signalling 24 . Among these pathways, the NF‐kB pathway is a major regulator of inflammation due to its ability to cause transcription of numerous genes involved in the inflammatory response 25–27 . Therefore, inhibition of NF‐κB signalling in DPFs should be continued throughout the resolution process.…”