Effect of salivary exosomal miR-25-3p on periodontitis with insulin resistance
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE189107 | GEO | 2021/11/20
REPOSITORIES: GEO
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Project description:Periodontitis is caused by an oral microbial dysbiosis-mediated imbalance of the local immune microenvironment, which is promoted by insulin resistance and obesity. The prevalence and severity of periodontitis is higher in patients with type 2 diabetes than in healthy individuals, possibly because of differences in immune responses. The level of glycemic control also affects the saliva profile, which may further promote periodontal disease in diabetes patients. Therefore, we compared the salivary exosomal miRNA profiles of patients with type 2 diabetes with those of healthy individuals, and we found that exosomal miR-25-3p in saliva is significantly enriched (by approximately 2-fold, p < 0.01) in obese patients with type 2 diabetes. We also identified CD69 mRNA as a miR-25-3p target that regulates both activation of γδ T cells and the inflammatory response. Knockdown of CD69 increased (by approximately 2-fold) interleukin-17A production of γδ T cells in vitro. To evaluate the role of exosomal miRNA on progression of periodontitis, we analyzed regional immune cells in both periodontal tissues and lymph nodes from mice with periodontitis. We found that diet-induced obesity increased the population of infiltrating pro-inflammatory immune cells in the gingiva and regional lymph nodes of these mice. Treatment with miR-25-3p inhibitors prevented the local in vivo inflammatory response in mice with periodontitis and diet-induced obesity. Finally, we showed that suppression of interleukin 17-mediated local inflammation by a miR-25-3p inhibitor alleviated (by approximately 34%) ligature-induced periodontal alveolar bone loss in mice. Taken together, these data suggest that exosomal miR-25-3p in saliva contributes to development and progression of diabetes-associated periodontitis. Discovery of additional miR-25-3p targets may provide critical insights into developing drugs to treat periodontitis by regulating γδ T cell-mediated local inflammation.
| S-EPMC8777127 | biostudies-literature
Project description:Effect of salivary exosomal miR-25-3p on periodontitis with insulin resistance
| PRJNA781584 | ENA
Project description:Treatment of periodontitis in people with diabetes remains challenging. Diabetes-enhanced oxidative stress is a primary cause of aggravation of periodontitis. The present study aimed to investigate the therapeutic potential of thioredoxin-1 (TRX1), an essential endogenous antioxidant protein, in the management of periodontitis with diabetes, as well as its role in modulating osteogenic differentiation. Our findings indicated that the production of reactive oxygen species (ROS) was elevated, while the expression of TRX1 was significantly reduced in the periodontal tissues of periodontitis mice with diabetes. Furthermore, knockdown of TRX1 in periodontal ligament stem cells (PDLSCs) resulted in the inhibition of osteogenic differentiation through disrupting Wnt/β-catenin signal pathway. However, this inhibition was restored upon administration of recombinant human TRX1 (rhTRX1). Importantly, rhTRX1 treatment decreased ROS generation, activated Wnt/β-catenin signal pathway and considerably promoted the alveolar bone repair of periodontitis mice with diabetes. These findings highlighted the crucial protective role of TRX1 in periodontitis with diabetes and suggested that it may serve as a potential therapeutic target for refractory periodontitis associated with oxidative stress.
2023-09-06 | GSE235930 | GEO
Project description:Using single cell-RNA sequencing, we reported structural and functional changes of gingival cellulome in diabetes-associated periodontitis, with the aim to identify distinct cell populations and functions involving in disease progression. We identified inflammation-related stromal and epithelial subpopulations that expanded in diabetes-associated periodontitis, creating distinct immune microenvironment that drives the progression of the disease.
2023-09-11 | GSE189922 | GEO
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.
2010-08-13 | E-GEOD-23586 | biostudies-arrayexpress
Project description:We report the application of high throughput Illumina sequencing for profiling of small RNAs in saliva of patients who were diagnosed with chronic periodontitis as compared to healthy controls. To date, there is no published literature on salivary microRNA profiling done using the high throughput next-generation sequencing analysis in patients diagnosed with chronic periodontitis. Also, this is the first study of its kind done in an Indian population. The objectives of the study were to profile microRNAs expressed in saliva of patients diagnosed with chronic periodontitis, to identify differentially expressed microRNAs between chronic periodontitis and healthy patients and to identify putative salivary microRNAs which can serve as biomarkers for periodontal disease.
2018-10-30 | GSE121910 | GEO
Project description:Dysbiosis of subgingival microbiome promotes the growth of periodontopathogens and the development of periodontitis, an irreversible chronic inflammatory disease. Untreated periodontitis leads to the destruction of connective tissues, alveolar bone resorption and ultimately to tooth loss. Periodontitis has been associated with inflammatory metabolic diseases such as type 2 diabetes. While periodontitis-induced inflammation is a key player in both, the development of subgingival microbiome dysbiosis and in the host-microbiome interaction, the effects of hyperglycemia on the regulation of the host genes controlling the inflammatory response and the host-microbiome interaction are still scarce. We investigated the impacts of a hyperglycemic microenvironment on the inflammatory response and gene expression of a gingival fibroblasts-macrophages coculture model stimulated with dysbiotic subgingival microbiomes. A coculture model composed of immortalized human gingival fibroblasts overlaid with U937 macrophages-likes cells were stimulated with subgingival microbiome collected from four healthy donors and four patients with periodontitis. Pro-inflammatory cytokines and matrix metalloproteinase were measured by a Luminex assay while the coculture RNA was submitted to a microarray analysis. Subgingival microbiomes were submitted to 16s rRNA gene sequencing. Data were analyzed by using an advanced multi-omics bioinformatic data integration model. Our results showed that krt76, krt27, pnma5, mansc4, rab41, thoc6, tm6sf2, and znf506 as well as the pro-inflammatory cytokines IL-1, GM-CSF, FGF2, IL-10, the metalloproteinases MMP3 and MMP8, and bacteria from the ASV 105, ASV 211, ASV 299, Prevotella, Campylobacter and Fretibacterium genera are key correlated variables contributing to periodontitis-induced inflammatory response in a hyperglycemic microenvironment. To conclude, our multi-omics integration analysis unveiled unique differentially interrelated bacterial genera, genes and pro-inflammatory cytokines involved in the regulation of the inflammatory response in a hyperglycemic microenvironment. These data also highlight the importance of considering hyperglycemic conditions in the development of new drugs or treatments for periodontal disease in link with type 2 diabetes.
2023-05-31 | GSE222883 | GEO
Project description:Diabetes and periodontitis, as widespread chronic diseases, often exacerbate each other's conditions. Non-surgical periodontal treatments can improve the oral and systemic health in these patients, with salivary proteins offering potential insights into disease mechanisms and treatment effectiveness. However, there is a lack of comprehensive data on salivary proteomics in this context. By assigning patients with diabetes-associated periodontitis to a test group (supragingival scaling, subgingival scraping and root planing) or a control group (supragingival scaling only), analyzing non-stimulated whole saliva samples using liquid chromatography-tandem mass spectrometry, and establishing the in vivo and in vitro models, we found significant differential expression of salivary proteins related to Apelin signaling pathway, hematopoietic cell profiling, stress response and immune regulation, identifying four candidate proteins: superoxide dismutase 1 (SOD1), profilin 1 (PFN1), S100 calcium-binding protein A11 (S100A11) and kallikrein-related peptidase 6 (KLK6). All four proteins were significantly elevated, with a combined area under the curve of 0.933, while SOD1 alone reached 0.915. Additionally, we observed high glucose and inflammatory conditions reduced SOD1 expression. In conclusion, SOD1 emerges as a promising regulatory target for managing diabetes and periodontitis by modulating the oral oxidative stress microenvironment.
2024-09-01 | PXD055453 |
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.
2010-08-13 | GSE23586 | GEO
Project description:We confirmed immune response as the key mechanism and provided solid evidence for novel genes (e.g., FCAR and CUX1) and distinct biological processes (e.g., endocytosis, cytokine production and apoptosis) as potentially new important factors/mechanisms contributing to chronic periodontitis pathogenesis.
2016-07-16 | GSE61490 | GEO