title: Upregulation of gingival tissue miR-200b in obese periodontitis subjects.
abstract: Increased local immune and inflammatory responses in obese individuals with periodontitis may explain the aggressive clinical presentation and altered treatment response when compared to that of normal weight subjects. Our goal was to identify any differences in microRNA (miRNA) expression profiles of gingival tissue in periodontitis when obesity is present, which may suggest novel molecular pathways that this miRNA network may affect. Total RNA was extracted from gingival tissue biopsies collected from normal weight and obese individuals with periodontitis; miRNA expression profiling was performed with Affymetrix GeneChip miRNA 3.0 arrays; and results were validated with quantitative reverse transcription polymerase chain reaction (qRT-PCR). In silico identification of previously confirmed miRNA gene targets was conducted through miRTarBase and miRWalk databases, and pathway enrichment analysis identified enriched miRNA gene sets. Expression of selected genes in the same biopsy samples was tested with qRT-PCR. The gingival tissue miRNA profile of obese patients, compared to that of normal weight patients, showed 13 upregulated and 22 downregulated miRNAs, among which miR-200b was validated by qRT-PCR to be significantly increased in obesity. Functional analysis of 51 experimentally validated miR-200b gene targets identified enrichment of genes involved in cell motility, differentiation, DNA binding, response to stimulus, and vasculature development pathways not previously identified in the obesity-specific disease profile. Furthermore, the expression of the miR-200b gene targets ZEB1/2, GATA2, and KDR was confirmed by qRT-PCR as being lower in obese patients with periodontitis versus normal weight patients, suggesting a role of miR-200b in regulation of a set of gene targets and biological pathways relevant to wound healing and angiogenesis. Functional studies to explore the role of miR-200b in the above processes may offer new insights on putative therapeutic targets for this group of patients.
authors: Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK a.kalea@ucl.ac.uk.
authors: A Z
authors: AZ
authors: Kalea
authors: Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.
authors: R
authors: R
authors: Hoteit
authors: Unit of Periodontology, Eastman Dental Institute, University College London, London, UK.
authors: J
authors: J
authors: Suvan
authors: Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.
authors: R C
authors: RC
authors: Lovering
authors: Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.
authors: J
authors: J
authors: Palmen
authors: Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.
authors: J A
authors: JA
authors: Cooper
authors: Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.
authors: V K
authors: VK
authors: Khodiyar
authors: Peninsula School of Dentistry, Plymouth University, Plymouth, UK.
authors: Z
authors: Z
authors: Harrington
authors: Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.
authors: S E
authors: SE
authors: Humphries
authors: Unit of Periodontology, Eastman Dental Institute, University College London, London, UK.
authors: F
authors: F
authors: D'Aiuto
mesh_terms: D000328:Adult; D001835:Body Weight; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D050989:GATA2 Transcription Factor / Q000032:analysis; D020869:Gene Expression Profiling; D005881:Gingiva / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000032:analysis; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D018919:Neovascularization, Physiologic / Q000235:genetics; D009765:Obesity / Q000235:genetics*; D010518:Periodontitis / Q000235:genetics*; D012097:Repressor Proteins / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014157:Transcription Factors / Q000032:analysis; D015854:Up-Regulation; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D018398:Homeodomain Proteins; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: angiogenesis; epithelial; microRNA-200b; obesity; periodontal disease; wound healing
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