Vascular endothelial growth factor-C promotes human mesenchymal stem cell migration via an ERK-and FAK-dependent mechanism.

Vascular endothelial cell growth factor-C (VEGF-C) is a member of the VEGF family and plays a role in various biological activities. VEGF-C enhances proliferation and migration of lymphatic endothelial cells and vascular endothelial cells through VEGF receptor 2 (VEGFR2) and/or receptor 3 (VEGFR3), and thereby induces lymphangiogenesis or angiogenesis. However, it remains unclear whether VEGF-C promotes the migration of mesenchymal stem cells (MSCs). Here, we investigated the effects of VEGF-C on the migration of MSCs and evaluated the underlying molecular mechanisms. VEGF-C treatment significantly induced the migration of MSCs, which is accompanied by the promotion of actin cytoskeletal reorganization and focal adhesion assembly. VEGF-C treatment enhanced the phosphorylation of VEGFR2 and VEGFR3 proteins in MSCs, and pretreatment with VEGFR2 and VEGFR3 kinase inhibitors effectively suppressed the VEGF-C-induced MSC migration. In addition, VEGF-C treatment promoted phosphorylation of ERK and FAK proteins in MSCs, and inhibition of VEGFR2 and VEGFR3 signaling pathways abolished the VEGF-C-induced activation of ERK and FAK proteins. Furthermore, treatment with ERK and FAK inhibitors suppressed VEGF-C-induced actin cytoskeletal reorganization and focal adhesion assembly, and then significantly inhibited MSCs migration. These results suggest that VEGF-C-induced MSC migration is mediated via VEGFR2 and VEGFR3, and follows the activation of the ERK and FAK signaling pathway. Thus, VEGF-C may be valuable in tissue regeneration and repair in MSC-based therapy.

Assessment of postoperative complications using E-PASS and APACHE II in patients undergoing oral and maxillofacial surgery.

BACKGROUND: The prediction of postoperative complications is important for oral and maxillofacial surgeons. We herein aimed to evaluate the efficacy of the Estimation of Physiologic Ability and Surgical Stress (E-PASS) and Acute Physiology, Age, and Chronic Health Evaluation (APACHE) II scoring systems to predict postoperative complications in patients undergoing oral and maxillofacial surgery. METHODS: Thirty patients (22 males, 8 females; mean age: 65.1 ± 12.9 years) who underwent major oral surgeries and stayed in the intensive care unit for postoperative management were enrolled in this study. Postoperative complications were discriminated according to the necessity of the therapeutic intervention by the Medical Department, i.e. according to the Clavien-Dingo classification. E-PASS and APACHE II scores as well as laboratory test values were compared between patients with/without postoperative complications. RESULTS: Postoperative complications were developed in seven patients. The comprehensive risk score (CRS: 1.13 ± 0.24) and APACHE II score (13.0 ± 2.58) were significantly higher in patients with postoperative complications than in those without ones (p < 0.01, p < 0.05, respectively). The CRS showed an appropriate discriminatory power for predicting postoperative complications (area under the curve: 0.814). Furthermore, a correlation was detected between APACHE II scores and postoperative data until C-reactive protein levels decreased to < 1.0 mg/L (r = 0.43, p < 0.05). CONCLUSION: The E-PASS and APACHE II scoring systems were both shown to be useful to predict postoperative complications after oral and maxillofacial surgery.

Glycolipids from spinach suppress LPS-induced vascular inflammation through eNOS and NK-κB signaling.

Glycolipids are the major constituent of the thylakoid membrane of higher plants and have a variety of biological and pharmacological activities. However, anti-inflammatory effects of glycolipids on vascular endothelial cells have not been elucidated. Here, we investigated the effect of glycolipids extracted from spinach on lipopolysaccharides (LPS)-induced endothelial inflammation and evaluated the underlying molecular mechanisms. Treatment with glycolipids from spinach had no cytotoxic effects on cultured human umbilical vein endothelial cells (HUVECs) and significantly blocked the expression of LPS-induced interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), and intracellular adhesion molecule-1 (ICAM-1) in them. Glycolipids treatment also effectively suppressed monocyte adhesion to HUVECs. Treatment with glycolipids inhibited LPS-induced NF-κB phosphorylation and nuclear translocation. In addition, glycolipids treatment significantly promoted endothelial nitric oxide synthase (eNOS) activation and nitric oxide (NO) production in HUVECs. Furthermore, glycolipids treatment blocked LPS-induced inducible NOS (iNOS) expression in HUVECs. Pretreatment with a NOS inhibitor attenuated glycolipids-induced suppression of NF-κB activation and adhesion molecule expression, and abolished the glycolipids-mediated suppression of monocyte adhesion to HUVECs. These results indicate that glycolipids suppress LPS-induced vascular inflammation through attenuation of the NF-κB pathway by increasing NO production in endothelial cells. These findings suggest that glycolipids from spinach may have a potential therapeutic use for inflammatory vascular diseases.

Vascular endothelial growth factor-C induces osteogenic differentiation of human mesenchymal stem cells through the ERK and RUNX2 pathway.

Vascular endothelial cell growth factor C (VEGF-C) is a member of the VEGF family and plays a role in a variety of biological activities including lymphangiogenesis, angiogenesis, and neurogenesis through VEGF receptor 2 (VEGFR2) and 3 (VEGFR3). However, it has not been elucidated whether VEGF-C promotes osteogenic differentiation. Herein, we investigated the effects of VEGF-C on osteogenic differentiation in human mesenchymal stem cells (MSCs) and evaluated the underlying molecular mechanisms. VEGF-C treatment significantly increased RUNX2 expression, and led to the promotion of osteogenic marker gene expression and mineralization of MSCs. VEGF-C treatment induced the phosphorylation of VEGFR2 and VEGFR3 in MSCs. Treatment with the VEGFR3-specific ligand VEGF-C156S also promoted MSC mineralization. Furthermore, co-treatment with VEGFR2 and VEGFR3 kinase inhibitors blocked VEGF-C-induced MSC mineralization. VEGF-C treatment activated ERK signaling in MSCs, and inhibition of ERK signaling effectively suppressed VEGF-C-induced RUNX2 expression and mineralization. These results indicate that VEGF-C-induced MSC osteogenesis is mediated through VEGFR2 and VEGFR3, and followed the activation of the ERK/RUNX2 signaling pathway.