Lymphatic growth factors are expressed in human gingiva and upregulated in gingival fibroblasts after stimulation. Issue 5 (31st May 2018)

• Record Type: Journal Article
• Authors: Bletsa, Athanasia; Abdalla, Hisham; Løes, Sigbjørn; Berggreen, Ellen
• Is Part Of: Journal of periodontology. Volume 89:Issue 5(2018)
• Page Start: 606
• Page End: 615
• Publication Date: 2018-05-31
• Subjects: fibroblast(s) -- gene expression -- gingivitis -- growth factors -- periodontitis -- vascular biology; Periodontics -- Periodicals; 617.632
• DOI: 10.1002/JPER.17-0400
• Languages: English
• ISSNs: 0022-3492

Abstract

Abstract: Background: The lymphatic growth factors vascular endothelial growth factor (VEGF)‐C and ‐D are important for maintenance and growth of lymphatic vessels (lymphangiogenesis), but their localization in human gingiva is unknown. This study investigated the expression of VEGF‐C and ‐D in human gingiva and isolated human gingival fibroblasts (HGFs). In addition, the localization of their main receptor VEGFR‐3 was explored. Methods: Non‐inflamed gingiva from six donors was used for immunohistochemistry or isolation of HGFs. HGFs were stimulated with either E.coli lipopolysaccharide (LPS) or IL‐6/soluble IL‐6 receptor (sIL‐6R) complex for 1, 6, and 24 hours. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to quantify the relative changes in gene expression of VEGF‐A, ‐C, and ‐D and enzyme‐linked immunosorbent assay (ELISA) for quantification of protein levels. Results: VEGF‐C, ‐D and VEGFR‐3 were seen in keratinocytes, blood vessels and in scattered single cells in gingiva. VEGFR‐3 was also found in lymphatic vessels and VEGF‐C in cells with fibroblastic appearance. Gene analysis showed no expression of VEGF‐D in the HGFs, but showed constitutive expression of VEGF‐C and ‐A. Stimulation of HGFs with LPS or IL‐6/sIL‐6R complex was followed by gene upregulation of VEGF‐C and ‐A and increased protein levels in cell culture supernatant ( P ≤0.05). Conclusions: The localization of VEGF‐C, ‐D, and VEGFR‐3 expression imply that signaling via VEGFR‐3 is linked to vascular homeostasis and keratinocyte function under normal conditions in gingiva. Inflammatory stimulation of HGFs upregulates VEGF‐C and ‐A expression and may contribute to angiogenesis and lymphangiogenesis.