Molecular Oral Microbiology最新文献

{"title":"NOD2 contributes to Parvimonas micra-induced bone resorption in diabetic rats with experimental periodontitis.","authors":"Ying-Yi Chen, Li Tan, Xiao-Lin Su, Ning-Xin Chen, Qiong Liu, Yun-Zhi Feng, Yue Guo","doi":"10.1111/omi.12467","DOIUrl":"https://doi.org/10.1111/omi.12467","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (T2DM) may affect the oral microbial community, exacerbating periodontal inflammation; however, its pathogenic mechanisms remain unclear. As nucleotide-binding oligomerization domain 2 (NOD2) plays a crucial role in the activation during periodontitis (PD), it is hypothesized that changes in the oral microbial community due to diabetes enhance periodontal inflammation through the activation of NOD2.</p><p><strong>Methods: </strong>We collected subgingival plaque from 180 subjects who were categorized into two groups based on the presence or absence of T2DM. The composition of oral microbiota was detected by 16S rRNA high-throughput sequencing. In animal models of PD with or without T2DM, we assessed alveolar bone resorption by micro-computerized tomography and used immunohistochemistry to detect NOD2 expression in alveolar bone. Primary osteoblasts were cultured in osteogenic induction medium with high or normal glucose and treated with inactivated bacteria. After 24 h of inactivated bacteria intervention, the osteogenic differentiation ability was detected by alkaline phosphatase (ALP) staining, and the expressions of NOD2 and interleukin-12 (IL-6) were detected by western blot.</p><p><strong>Results: </strong>The relative abundance of Parvimonas and Filifactor in the T2DM group was increased compared to the group without T2DM. In animal models, alveolar bone mass was decreased in PD, particularly in T2DM with PD (DMPD) group, compared to controls. Immunohistochemistry revealed NOD2 in osteoblasts from the alveolar bone in both the PD group and DMPD group, especially in the DMPD group. In vitro, intervention with inactivated Parvimonas significantly reduced ALP secretion of primary osteoblasts in high glucose medium, accompanied by increased expression of NOD2 and IL-6.</p><p><strong>Conclusions: </strong>The results suggest that T2DM leading to PD may be associated with the activation of NOD2 by Parvimonas.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover Image, Volume 39, Issue 3","authors":"","doi":"10.1111/omi.12468","DOIUrl":"https://doi.org/10.1111/omi.12468","url":null,"abstract":"","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141063895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A cleaved adhesin DNA vaccine targeting dendritic cell against Porphyromonas gingivalis–induced periodontal disease","authors":"Xin Fan, Peng‐Yu Qu, Ke‐Feng Luan, Chen‐Yu Sun, Hui‐Ping Ren, Xue‐Hui Sun, Jing Lan","doi":"10.1111/omi.12465","DOIUrl":"https://doi.org/10.1111/omi.12465","url":null,"abstract":"BackgroundArg‐gingipain A (RgpA) is the primary virulence factor of <jats:italic>Porphyromonas gingivalis</jats:italic> and contains hemagglutinin adhesin (HA), which helps bacteria adhere to cells and proteins. Hemagglutinin's functional domains include cleaved adhesin (CA), which acts as a hemagglutination and hemoglobin‐binding actor. Here, we confirmed that the HA and CA genes are immunogenic, and using adjuvant chemokine to target dendritic cells (DCs) enhanced protective autoimmunity against <jats:italic>P. gingivalis</jats:italic>–induced periodontal disease.MethodsC57 mice were immunized prophylactically with pVAX1‐CA, pVAX1‐HA, pVAX1, and phosphate‐buffered saline (PBS) through intramuscular injection every 2 weeks for a total of three administrations before <jats:italic>P. gingivalis</jats:italic>–induced periodontitis. The DCs were analyzed using flow cytometry and ribonucleic acid sequencing (RNA‐seq) transcriptomic assays following transfection with CA lentivirus. The efficacy of the co‐delivered molecular adjuvant CA DNA vaccine was evaluated in vivo using flow cytometry, immunofluorescence techniques, and micro‐computed tomography.ResultsAfter the immunization, both the pVAX1‐CA and pVAX1‐HA groups exhibited significantly elevated <jats:italic>P. gingivalis</jats:italic>–specific IgG and IgG1, as well as a reduction in bone loss around periodontitis‐affected teeth, compared to the pVAX1 and PBS groups (<jats:italic>p </jats:italic>&lt; 0.05). The expression of CA promoted the secretion of HLA, CD86, CD83, and DC‐specific intercellular adhesion molecule‐3‐grabbing non‐integrin (DC‐SIGN) in DCs. Furthermore, the RNA‐seq analysis revealed a significant increase in the chemokine (C–C motif) ligand 19 (<jats:italic>p </jats:italic>&lt; 0.05). A notable elevation in the quantities of DCs co‐labeled with CD11c and major histocompatibility complex class II, along with an increase in interferon‐gamma (IFN‐γ) cells, was observed in the inguinal lymph nodes of mice subjected to CCL19‐CA immunization. This outcome effectively illustrated the preservation of peri‐implant bone mass in rats afflicted with <jats:italic>P. gingivalis</jats:italic>–induced peri‐implantitis (<jats:italic>p</jats:italic> &lt; 0.05).ConclusionsThe co‐administration of a CCL19‐conjugated CA DNA vaccine holds promise as an innovative and targeted immunization strategy against <jats:italic>P. gingivalis</jats:italic>–induced periodontitis and peri‐implantitis.","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140840835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Streptococcus salivarius ameliorates the destructive effect on the epithelial barrier by inhibiting the growth of Prevotella melaninogenica via metabolic acid production","authors":"Pingyi Zhu, Ruru Shao, Pan Xu, Ruowen Zhao, Chen Zhao, Jian Fei, Yuan He","doi":"10.1111/omi.12464","DOIUrl":"https://doi.org/10.1111/omi.12464","url":null,"abstract":"BackgroundOral lichen planus (OLP) is one of the most common oral mucosal diseases, exhibiting a higher prevalence in women than men, but its pathogenesis is still unclear. Current research suggests that microbial dysbiosis may play an important role in the pathogenesis of OLP. Our previous research has found that the increase of <jats:italic>Prevotella melaninogenica</jats:italic> and decrease of <jats:italic>Streptococcus salivarius</jats:italic> have been identified as a potential pathogenic factor in OLP. Consequently, the objective of this study is to examine whether <jats:italic>S. salivarius</jats:italic> can counteract the detrimental effects of <jats:italic>P. melaninogenica</jats:italic> on the integrity of the epithelial barrier function.Materials and methodsEpithelial barrier disruption was induced by <jats:italic>P. melaninogenica</jats:italic> in human keratinocytes (HaCaT cells). HaCaT cells were pretreated with <jats:italic>S. salivarius</jats:italic>(MOI = 20) or cell‐free supernatant for 3 h, followed by treatment with <jats:italic>P. melaninogenica</jats:italic> (MOI = 5) for 3 h. The epithelial barrier integrity of HaCaT cells was detected by FD4 permeability. The mRNA level of tight junction protein was detected by quantitative real‐time polymerase chain reaction (PCR). Immunofluorescence and Western Blot were used to detect the protein expression of zonula occludin‐1 (ZO‐1). The serial dilution‐spotting assay was applied to monitor the viability of <jats:italic>P. melaninogenica</jats:italic> at the end of 8 and 24 h incubation.ResultsChallenge by <jats:italic>P. melaninogenica</jats:italic> decreased the levels of tight junction proteins, including occludin, ZO‐1, and claudin in HaCaT cells. <jats:italic>S. salivarius</jats:italic> or its cell‐free supernatant inhibited the down‐regulation of ZO‐1 mRNA and protein expression levels induced by <jats:italic>P. melaninogenica</jats:italic> and thus improved the epithelial barrier function. The inhibitory effect of the cell‐free supernatant of <jats:italic>S. salivarius</jats:italic> on the growth of <jats:italic>P. melaninogenica</jats:italic> is associated with metabolic acid production rather than with bacteriocins and hydrogen peroxide.ConclusionsThese results suggest that live <jats:italic>S. salivarius</jats:italic> or its cell‐free supernatant significantly ameliorated the disruption of epithelial tight junctions induced by <jats:italic>P. melaninogenica</jats:italic>, likely through the inhibition of <jats:italic>P. melaninogenica</jats:italic> growth mediated by metabolic acid production.","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140840738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metronidazole may display anti‐inflammatory features in periodontitis treatment: A scoping review","authors":"Lina J Suárez, Roger M Arce, Cristiane Gonçalves, Camila Pinheiro Furquim, Nidia Castro Dos Santos, Belén Retamal‐Valdes, Magda Feres","doi":"10.1111/omi.12459","DOIUrl":"https://doi.org/10.1111/omi.12459","url":null,"abstract":"AimMetronidazole (MTZ) is an antimicrobial agent used to treat anaerobic infections. It has been hypothesized that MTZ may also have anti‐inflammatory properties, but the evidence is limited and has not been previously reviewed. Thus, this scoping review aimed to answer the following question: “What is the evidence supporting anti‐inflammatory properties of metronidazole that are not mediated by its antimicrobial effects?”MethodsA scoping review was conducted according to the PRISMA‐ScR statement. Five databases were searched up to January 2023 for studies evaluating the anti‐inflammatory properties of MTZ used as monotherapy for treating infectious and inflammatory diseases.ResultsA total of 719 records were identified, and 27 studies (21 in vivo and 6 in vitro) were included. The studies reported experimental evidence of MTZ anti‐inflammatory effects on (1) innate immunity (barrier permeability, leukocyte adhesion, immune cell populations), (2) acquired immunity (lymphocyte proliferation, T‐cell function, cytokine profile), and (3) wound healing/resolution of inflammation.ConclusionTaken together, this scoping review supported a potential anti‐inflammatory effect of MTZ in periodontitis treatment. We recommend that future clinical studies should be conducted to evaluate specific MTZ anti‐inflammatory pathways in the treatment of periodontitis.","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140602290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tannerella forsythia scavenges Fusobacterium nucleatum secreted NOD2 stimulatory molecules to dampen oral epithelial cell inflammatory response.","authors":"Rajendra P Settem, Angela Ruscitto, Sreedevi Chinthamani, Kiyonobu Honma, Ashu Sharma","doi":"10.1111/omi.12429","DOIUrl":"10.1111/omi.12429","url":null,"abstract":"<p><p>The oral organism Tannerella forsythia is auxotrophic for peptidoglycan amino sugar N-acetylmuramic acid (MurNAc). It survives in the oral cavity by scavenging MurNAc- and MurNAc-linked peptidoglycan fragments (muropeptides) secreted by co-habiting bacteria such as Fusobacterium nucleatum with which it forms synergistic biofilms. Muropeptides, MurNAc-l-Ala-d-isoGln (MDP, muramyl dipeptide) and d-γ-glutamyl-meso-DAP (iE-DAP dipeptide), are strong immunostimulatory molecules that activate nucleotide oligomerization domain (NOD)-like innate immune receptors and induce the expression of inflammatory cytokines and antimicrobial peptides. In this study, we utilized an in vitro T. forsythia-F. nucleatum co-culture model to determine if T. forsythia can selectively scavenge NOD ligands from the environment and impact NOD-mediated inflammation. The results showed that NOD-stimulatory molecules were secreted by F. nucleatum in the spent culture broth, which subsequently induced cytokine and antimicrobial peptide expression in oral epithelial cells. In the spent broth from T. forsythia-F. nucleatum co-cultures, the NOD-stimulatory activity was significantly reduced. These data indicated that F. nucleatum releases NOD2-stimulatory muropeptides in the environment, and T. forsythia can effectively scavenge the muropeptides released by co-habiting bacteria to dampen NOD-mediated host responses. This proof-of-principle study demonstrated that peptidoglycan scavenging by T. forsythia can impact the innate immunity of oral epithelium by dampening NOD activation.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10792118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9824215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel SUCNR1 inhibitor alleviates dysbiosis through inhibition of host responses without direct interaction with host microbiota.","authors":"Scott C Thomas, Yuqi Guo, Fangxi Xu, Deepak Saxena, Xin Li","doi":"10.1111/omi.12431","DOIUrl":"10.1111/omi.12431","url":null,"abstract":"<p><p>Type 2 diabetes (T2D) is a chronic metabolic disorder in which insulin resistance and impaired insulin secretion result in altered metabolite balance, specifically elevated levels of circulating glucose and succinate, which increases the risk of many pathologies, including periodontitis. Succinate, a tricarboxylic acid (TCA) cycle intermediate, can be produced and metabolized by both host cells and host microbiota, where elevated levels serve as an inflammation and pathogen threat signal through activating the succinate G protein-coupled receptor, SUCNR1. Modulating succinate-induced SUCNR1 signaling remains a promising therapeutic approach for pathologies resulting in elevated levels of succinate, such as T2D and periodontitis. Here, we demonstrate hyperglycemia and elevated intracellular succinate in a T2D mouse model and determine gut microbiome composition. Drawing on previous work demonstrating the ability of a novel SUCNR1 antagonist, compound 7a, to block inflammation and alleviate dysbiosis in a mouse model, we examined if compound 7a has an impact on the growth and virulence gene expression of bacterial and fungal human microbiota in vitro, and if 7a could reduce bone loss in a periodontitis-induced mouse model. T2D mice harbored a significantly different gut microbiome, suggesting the altered metabolite profile of T2D causes shifts in host-microbial community structure, with enrichment in succinate producers and consumers and mucin-degrading bacteria. Bacterial and fungal cultures showed that 7a did not influence growth or virulence gene expression, suggesting the therapeutic effects of 7a are a direct result of 7a interacting with host cells and that alterations in microbial community structure are driven by reduced host SUCNR1 signaling. This work further suggests that targeting SUCNR1 signaling is a promising therapeutic approach in metabolic, inflammatory, or immune disorders with elevated succinate levels.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10939988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10266107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional profile of oral plaque microbiome: Further insight into the bidirectional relationship between type 2 diabetes and periodontitis.","authors":"Nicoletta Favale, Roberto Farina, Alberto Carrieri, Anna Simonelli, Mattia Severi, Silvia Sabbioni, Leonardo Trombelli, Chiara Scapoli","doi":"10.1111/omi.12418","DOIUrl":"10.1111/omi.12418","url":null,"abstract":"<p><p>Increasing evidence support the association between the oral microbiome and human systemic diseases. This association may be attributed to the ability of many oral microbes to influence the inflammatory microenvironment. Herein, we focused our attention on the bidirectional relationship between periodontitis and type 2 diabetes using high-resolution whole metagenomic shotgun analysis to explore the composition and functional profile of the subgingival microbiome in diabetics and non-diabetics subjects with different periodontal conditions. In the present study, the abundance of metabolic pathways encoded by oral microbes was reconstructed from the metagenome, and we identified a set of dysregulated metabolic pathways significantly enriched in the periodontitis and/or diabetic patients. These pathways were mainly involved in branched and aromatic amino acids metabolism, fatty acid biosynthesis and adipocytokine signaling pathways, ferroptosis and iron homeostasis, nucleotide metabolism, and finally in the peptidoglycan and lipopolysaccharides synthesis. Overall, the results of the present study provide evidence in favor of the hypothesis that during the primary inflammatory challenge, regardless of whether it is induced by periodontitis or diabetes, endotoxemia and/or the release of inflammatory cytokines cause a change in precursor and/or in circulating innate immune cells. Dysbiosis and inflammation, also via oral-gut microbiome axis or adipose tissue, reduce the efficacy of the host immune response, while fueling inflammation and can induce that metabolic/epigenetic reprogramming of chromatin accessibility of genes related to the immune response. Moreover, the presence of an enhanced ferroptosis and an imbalance in purine/pyrimidine metabolism provides new insights into the role of ferroptotic death in this comorbidity.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9551872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fusobacterium nucleatum triggers senescence phenotype in gingival epithelial cells.","authors":"Emmanuel Albuquerque-Souza, Benjamin Shelling, Min Jiang, Xia-Juan Xia, Kantapon Rattanaprukskul, Sinem Esra Sahingur","doi":"10.1111/omi.12432","DOIUrl":"10.1111/omi.12432","url":null,"abstract":"<p><p>The prevalence of periodontitis increases with physiological aging. However, whether bacteria associated with periodontal diseases foster aging and the mechanisms by which they may do so are unknown. Herein, we hypothesize that Fusobacterium nucleatum, a microorganism associated with periodontitis and several other age-related disorders, triggers senescence, a chief hallmark of aging responsible to reduce tissue repair capacity. Our study analyzed the senescence response of gingival epithelial cells and their reparative capacity upon long-term exposure to F. nucleatum. Specifically, we assessed (a) cell cycle arrest by analyzing the cyclin-dependent kinase inhibitors p16^INK4a and p14^ARF and their downstream cascade (pRb, p53, and p21) at both gene and protein levels, (b) lysosomal mediated dysfunction by using assays targeting the expression and activity of the senescence-associated β-galactosidase (SA-β-Gal) enzyme, and (c) nuclear envelope breakdown by assessing the expression of Lamin-B1. The consequences of the senescence phenotype mediated by F. nucleatum were further assessed using wound healing assays. Our results revealed that prolonged exposure to F. nucleatum promotes an aging-like phenotype as evidenced by the increased expression of pro-senescence markers (p16^INK4a , p21, and pRb) and SA-β-Gal activity and reduced expression of the counter-balancing cascade (p14^ARF and p53) and Lamin-B1. Furthermore, we also noted impaired wound healing capacity of gingival epithelial cells upon prolong bacterial exposure, which was consistent with the senescence-induced phenotype. Together, our findings provide a proof-of-concept evidence that F. nucleatum triggers a pro-senescence response in gingival epithelial cells. This might affect periodontal tissue homeostasis by reducing its repair capacity and, consequently, increasing susceptibility to periodontitis during aging.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10939983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10339538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GroEL of Porphyromonas gingivalis-induced microRNAs accelerate tumor neovascularization by downregulating thrombomodulin expression in endothelial progenitor cells.","authors":"Feng-Yen Lin, Yi-Ting Tsai, Chun-Yao Huang, Ze-Hao Lai, Chien-Sung Tsai, Chun-Ming Shih, Cheng-Yen Lin, Yi-Wen Lin","doi":"10.1111/omi.12415","DOIUrl":"10.1111/omi.12415","url":null,"abstract":"<p><p>We found that GroEL in Porphyromonas gingivalis accelerated tumor growth and increased mortality in tumor-bearing mice; GroEL promoted proangiogenic function, which may be the reason for promoting tumor growth. To understand the regulatory mechanisms by which GroEL increases the proangiogenic function of endothelial progenitor cells (EPCs), we explored in this study. In EPCs, MTT assay, wound-healing assay, and tube formation assay were performed to analyze its activity. Western blot and immunoprecipitation were used to study the protein expression along with next-generation sequencing for miRNA expression. Finally, a murine tumorigenesis animal model was used to confirm the results of in vitro. The results indicated that thrombomodulin (TM) direct interacts with PI₃ K/Akt to inhibit the activation of signaling pathways. When the expression of TM is decreased by GroEL stimulation, molecules in the PI₃ K/Akt signaling axis are released and activated, resulting in increased migration and tube formation of EPCs. In addition, GroEL inhibits TM mRNA expression by activating miR-1248, miR-1291, and miR-5701. Losing the functions of miR-1248, miR-1291, and miR-5701 can effectively alleviate the GroEL-induced decrease in TM protein levels and inhibit the proangiogenic abilities of EPCs. These results were also confirmed in animal experiments. In conclusion, the intracellular domain of the TM of EPCs plays a negative regulatory role in the proangiogenic capabilities of EPCs, mainly through direct interaction between TM and PI₃ K/Akt to inhibit the activation of signaling pathways. The effects of GroEL on tumor growth can be reduced by inhibiting the proangiogenic properties of EPCs through the inhibition of the expression of specific miRNAs.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9474999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}