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Int Endod J. 2019 Jul 3. doi: 10.1111/iej.13179. [Epub ahead of print]

VEGFA/VEGFR2 axis promotes human dental pulp stem cell migration via the FAK/PI3K/Akt and p38 MAPK signalling pathways.

Author information

1
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, P.R. China.

Abstract

AIM:

To investigate the effects of vascular endothelial growth factor A (VEGFA) and the underlying molecular mechanisms in 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 utilised 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 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 higher than those in the control groups (P < 0.05). VEGFA 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 inhibited with drug inhibitors such as PF573228, LY294002, SB203580 or SU5416 (P < 0.05). These signalling pathways activated by VEGFA stimulation were suppressed by pre-treatment with inhibitor of VEGFR2 (SU5416) or transfection with siRNA of VRGFR2 (P < 0.05) but not VEGFR1 siRNA.

CONCLUSIONS:

VEGFA/VEGFR2 axis promoted hDPSCs migration via the FAK/PI3K/Akt and p38 MAPK signalling pathways. These findings reveal a novel molecular mechanism of cell migration of hDPSCs, which may contribute to the remodelling of pulp and dentine. This article is protected by copyright. All rights reserved.

KEYWORDS:

VEGFA ; DPSCs; FAK/PI3K/Akt; VEGFR2; migration; p38

PMID:
31267530
DOI:
10.1111/iej.13179

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