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Fibroblast VEGF-receptor 1 expression as molecular target in periodontitis
Ohu Univ, Sch Pharmaceut Sci, Dept Biochem, Misumido 31-1, Koriyama, Fukushima 9638611, Japan..
Nihon Univ, Sch Dent, Dept Biochem, Tokyo 101, Japan..
Ohu Univ, Sch Dent, Dept Morphol Biol, Misumido 31-1, Koriyama, Fukushima 9638611, Japan..
Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan.;Univ Tokyo, Fac Med, Tokyo 113, Japan..
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2016 (English)In: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 43, no 2, 128-137 p.Article in journal (Refereed) Published
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Abstract [en]

AimDegradation of extracellular matrices is an integral part in periodontitis. For antagonizing this pathophysiological mechanism, we aimed at identifying gene expression profiles in disease progression contributing periodontitis-associated fibroblasts (PAFs) versus normal gingival fibroblasts to determine their molecular repertoire, and exploit it for therapeutic intervention. Materials and MethodsApplying an exploratory analysis using a small number of microarrays in combination with a three dimensional (3D) invitro culture model that incorporates some aspects of periodontitis, PAFs were initially characterized by gene-expression analyses, followed by targeted gene down-regulation and pharmacological intervention in vitro. Further, immunohistochemistry was applied for phosphorylation analyses in tissue specimens. ResultsPAFs were characterized by 42 genes being commonly up-regulated >1.5-fold, and by five genes that were concordantly down-regulated (<0.7-fold). Expression of vascular endothelial growth factor (VEGF)-receptor 1 (Flt-1) was highly enhanced, and was thus further explored in invitro culture models of periodontal fibroblasts without accounting for the microbiome. Phosphorylation of the VEGF-receptor 1 was enhanced in PAFs. Receptor inhibition by a specific VEGF-receptor inhibitor or intrinsic down-regulation by RNAi of the VEGF-receptor kinase in 3D gel cultures resulted in significant reduction in collagen degradation associated with increased tissue inhibitor of metalloproteinase expression, suggesting that Flt-1 may contribute to periodontitis. ConclusionBased on the finding that VEGF-receptor kinase inhibition impaired collagen degradation pathways, Flt-1 may represent a candidate for therapeutic approaches in periodontitis.

Place, publisher, year, edition, pages
2016. Vol. 43, no 2, 128-137 p.
Keyword [en]
fibroblasts, Flt-1, gene expression, gingiva, periodontal disease, vascular endothelial growth factor
National Category
Dentistry Surgery
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URN: urn:nbn:se:uu:diva-283794DOI: 10.1111/jcpe.12495ISI: 000371828300004PubMedID: 26932322OAI: oai:DiVA.org:uu-283794DiVA: diva2:919600
Available from: 2016-04-14 Created: 2016-04-14 Last updated: 2017-11-30Bibliographically approved

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Micke, Patrick

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