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RSPO4 is a potential risk gene of stages III–IV, grade C periodontitis through effects on innate immune response and oral barrier integrity

ABSTRACT: RSPO4 is a potential risk gene of stages III–IV, grade C periodontitis through effects on innate immune response and oral barrier integrity

PROVIDER: PRJNA922102 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23023955_1.fastq.gz	Fastqsanger.gz
	SRR23023955_2.fastq.gz	Fastqsanger.gz
	SRR23023956_1.fastq.gz	Fastqsanger.gz
	SRR23023956_2.fastq.gz	Fastqsanger.gz
	SRR23023957_1.fastq.gz	Fastqsanger.gz

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RSPO4 is a potential risk gene of stages III–IV, grade C periodontitis through effects on innate immune response and oral barrier integrity

Project description:Aim R-spondin 4 (RSPO4) is a suggestive risk gene of stage III–IV, grade C periodontitis and upregulated in gingiva of mice resistant to bacteria-induced alveolar bone loss. We aimed to replicate the association, identify and characterize the putative causal variant(s) and molecular effects, and understand the downstream effects of RSPO4 upregulation. Materials and Methods We performed a two-step association study for RSPO4 with imputed genotypes of a German–Dutch (896 stage III–IV, grade C periodontitis cases, 7104 controls) and Spanish sample (441 cases and 1141 controls). We analysed the allelic effects on transcription factor binding sites with reporter gene and antibody electrophoretic mobility shift assays. We used CRISPR/dCas9 activation and RNA sequencing to pinpoint RSPO4 as the target gene and to analyse downstream effects. Results RSPO4 was associated with periodontitis (rs6056178, pmeta = 4.6 × 10−5). rs6056178 contains a GATA-binding motif. The rs6056178 T-allele abolished reporter activity (p = .004) and reduced GATA binding (−14.5%). CRISPRa of the associated region increased RSPO4 expression (25.8 ± 6.5-fold, p = .003). RSPO4 activation showed strongest induction of Gliomedin (439-fold) and Mucin 21 (178-fold) and of the gene set “response to interferon-alpha” (area under the curve [AUC] = 0.8, p < 5 × 10−6). The most repressed gene set was “extracellular matrix interactions” (AUC = 0.8, padj = .00016). Conclusion RSPO4 is a potential periodontitis risk gene and modifies host defence and barrier integrity.

2023-01-09 | GSE222437 | GEO

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Project description:Apical periodontitis

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Transcription profiling of human grade II astrocytic tumor (astrocytomas) vs grade IV tumors (glioblastoma)

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Fibroblast VEGF-receptor 1 expression as molecular target in periodontitis

Project description:To identify gene expression profiles in those periodontitis-associated fibroblasts (PAFs) versus normal gingival fibroblasts to determine their molecular repertoire, and exploit it for therapeutic intervention. We collected RNA from 4 paired PAF and non PAF from patients with periodontitis

2015-03-11 | E-GEOD-66771 | biostudies-arrayexpress

Transcriptome of healthy gingival tissue in aggressive periodontitis

Project description:This study evaluated the transcriptome of healthy gingival tissue in patients with a history of generalized aggressive periodontitis (GAgP) and chronic periodontitis (CP) and in subjects with no history of periodontitis (H), using microarray analysis.

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Altered gene expressions of leukocyte transendothelial migration and cell communication pathways in periodontitis-affected gingival tissues

Project description:Gene expressions relate to the pathogenesis of periodontitis and have a crucial role in local tissue destruction and susceptibility to the disease. The aims of the present study were to explore comprehensive gene expressions/transcriptomes in periodontitis-affected gingival tissues, and to identify specific biological processes. The purpose of the present study was 1) to compare comprehensive gene expression/transcriptomes of periodontitis-affected gingival tissues with those of healthy tissues by using microarray and data mining technologies, and 2) to analyze significantly differentially expressed genes which belong to pathological pathways in periodontitis by qRT-PCR. Two distinct gingival samples including healthy and periodontal-affected gingiva were taken from 3 patients with severe chronic periodontitis. Total RNAs from 6 gingival tissue samples were used for microarray and data-mining analyses. Comparisons, gene ontology, and pathway frequency analyses were performed and identified significant biological pathways in periodontitis. Quantitative reverse transcription real-time polymerase chain reaction (qRT-PCR) analyse using 14 chronic periodontitis patients including 3 patients listed above and 14 healthy individuals showed 9 differentially expressed genes in leukocyte migration and cell communication pathways.

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