Vascular endothelial growth factor A/Vascular endothelial growth factor receptor 2 axis promotes human dental pulp stem cell migration via the FAK/PI3K/Akt and p38 MAPK signalling pathways

作者：X. G. Sun, Liuyan Meng, Weiwei Qiao, Ruhui Yang, Qian Gao, Yao Peng, Zhuan Bian · 发表于：International Endodontic Journal · 年份：2019 · DOI：10.1111/iej.13179 · 被引用次数：39 · 研究领域：Endodontics and Root Canal Treatments、Corneal Surgery and Treatments、Proteoglycans and glycosaminoglycans research

AIM: To investigate the effects of vascular endothelial growth factor A (VEGFA) and the underlying molecular mechanisms on the migration of human dental pulp stem cells (hDPSCs). METHODOLOGY: The expression of VEGFA in inflammatory pulp tissue and lipopolysaccharide (LPS)-stimulated dental pulp cells was examined by immunofluorescence staining and qRT-PCR. The migration of hDPSCs was detected using transwell migration and wound healing assays. The activation of FAK, PI3K, Akt and p38 signalling was evaluated by Western blot analysis. Silence RNA (siRNA) technology was utilized to knockdown the expression of VEGFR1 (Flt-1) and VEGFR2 (Flk-1/KDR). PF573228 (inhibitor of FAK), LY294002 (inhibitor of PI3K), SB203580 (inhibitor of p38) and SU5416 (inhibitor of VEGFR2) were employed to investigate the effect of VEGFA on the migratory mechanism of hDPSCs. Data were analysed statistically using the Student's t-test or one-way ANOVA. RESULTS: The expression levels of VEGFA in inflammatory pulp tissue in vivo and LPS-stimulated dental pulp cells in vitro were significantly greater than those in the control groups (P < 0.05). Vascular endothelial growth factor A promoted the migration of hDPSCs in a concentration-dependent manner. Several signalling pathways, including FAK, PI3K, Akt and p38, were activated by VEGFA in a dose- and time-dependent manner in hDPSCs. The VEGFA-induced migration of hDPSCs was significantly inhibited with drug inhibitors such as PF573228, LY294002, SB203580 o...