Extracellular Vesicles Derived From Lipopolysaccharide‐Challenged Gingival Fibroblast Reveal Distinct miRNA Expression Patterns Associated With Reduced Cancer Survival
ABSTRACT Objectives Periodontitis is a prevalent inflammatory disease with established systemic implications. Extracellular vesicles (EVs) have emerged as key mediators of intercellular communication, potentially linking periodontitis to systemic diseases. However, the molecular cargo of EVs from in...
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| Format: | Article |
| Language: | English |
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Wiley
2025-02-01
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| Series: | Clinical and Experimental Dental Research |
| Online Access: | https://doi.org/10.1002/cre2.70099 |
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| author | Daniel Diehl Charlotte Lauren Brauer Hagen S. Bachmann Daniel Pembaur Patrick Philipp Weil Anton Friedmann |
| author_facet | Daniel Diehl Charlotte Lauren Brauer Hagen S. Bachmann Daniel Pembaur Patrick Philipp Weil Anton Friedmann |
| author_sort | Daniel Diehl |
| collection | DOAJ |
| description | ABSTRACT Objectives Periodontitis is a prevalent inflammatory disease with established systemic implications. Extracellular vesicles (EVs) have emerged as key mediators of intercellular communication, potentially linking periodontitis to systemic diseases. However, the molecular cargo of EVs from inflamed periodontal cells remains poorly characterized. This study investigates the EV cargo of human gingival fibroblasts (hGF‐hTERT) following lipopolysaccharide (LPS) stimulation and explores their potential role in cancer progression. Materials and Methods EVs were isolated from LPS‐treated and untreated fibroblasts via ultracentrifugation. Dynamic light scattering and scanning electron microscopy characterized EV size and morphology. RNA sequencing identified differentially expressed miRNAs, validated by qPCR. Functional pathway enrichment and in‐silico analyses using The Cancer Genome Atlas (TCGA) were performed to assess EV‐associated miRNA impact on tumorigenesis. Results EV size and concentration remained unchanged after LPS stimulation. However, LPS‐derived EVs exhibited a 2.6‐fold increase in miRNA content, with three significantly upregulated miRNAs: miR‐146a‐5p, miR‐486‐5p, and miR‐451a. Functional enrichment analysis revealed their involvement in inflammation, immune modulation, and cancer pathways. In vitro, LPS‐derived EVs significantly enhanced prostate cancer (LnCap) cell proliferation. TCGA analysis linked the upregulated miRNAs to poor cancer prognosis. Conclusions LPS stimulation alters the miRNA cargo of gingival fibroblast‐derived EVs, enhancing pathways associated with inflammation and cancer progression. These findings suggest a mechanistic role for periodontal EVs in systemic disease pathogenesis, warranting further investigation into their diagnostic and therapeutic potential. |
| format | Article |
| id | doaj-art-221bf89f68cc48afbd7584520b140f5e |
| institution | DOAJ |
| issn | 2057-4347 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Experimental Dental Research |
| spelling | doaj-art-221bf89f68cc48afbd7584520b140f5e2025-08-20T03:18:41ZengWileyClinical and Experimental Dental Research2057-43472025-02-01111n/an/a10.1002/cre2.70099Extracellular Vesicles Derived From Lipopolysaccharide‐Challenged Gingival Fibroblast Reveal Distinct miRNA Expression Patterns Associated With Reduced Cancer SurvivalDaniel Diehl0Charlotte Lauren Brauer1Hagen S. Bachmann2Daniel Pembaur3Patrick Philipp Weil4Anton Friedmann5Department of Periodontology, School of Dentistry, Faculty of Health Witten/Herdecke University Witten GermanyDepartment of Periodontology, School of Dentistry, Faculty of Health Witten/Herdecke University Witten GermanyCenter for Biomedical Education and Research (ZBAF), Institute of Pharmacology and Toxicology, Faculty of Health Witten/Herdecke University Witten GermanyCenter for Biomedical Education and Research (ZBAF), Institute of Biochemistry and Molecular Medicine, Faculty of Health Witten/Herdecke University Witten GermanyCentre for Biomedical Education and Research (ZBAF), Institute for Clinical Molecular Genetics and Epigenetics, Faculty of Health Witten/Herdecke University Witten GermanyDepartment of Periodontology, School of Dentistry, Faculty of Health Witten/Herdecke University Witten GermanyABSTRACT Objectives Periodontitis is a prevalent inflammatory disease with established systemic implications. Extracellular vesicles (EVs) have emerged as key mediators of intercellular communication, potentially linking periodontitis to systemic diseases. However, the molecular cargo of EVs from inflamed periodontal cells remains poorly characterized. This study investigates the EV cargo of human gingival fibroblasts (hGF‐hTERT) following lipopolysaccharide (LPS) stimulation and explores their potential role in cancer progression. Materials and Methods EVs were isolated from LPS‐treated and untreated fibroblasts via ultracentrifugation. Dynamic light scattering and scanning electron microscopy characterized EV size and morphology. RNA sequencing identified differentially expressed miRNAs, validated by qPCR. Functional pathway enrichment and in‐silico analyses using The Cancer Genome Atlas (TCGA) were performed to assess EV‐associated miRNA impact on tumorigenesis. Results EV size and concentration remained unchanged after LPS stimulation. However, LPS‐derived EVs exhibited a 2.6‐fold increase in miRNA content, with three significantly upregulated miRNAs: miR‐146a‐5p, miR‐486‐5p, and miR‐451a. Functional enrichment analysis revealed their involvement in inflammation, immune modulation, and cancer pathways. In vitro, LPS‐derived EVs significantly enhanced prostate cancer (LnCap) cell proliferation. TCGA analysis linked the upregulated miRNAs to poor cancer prognosis. Conclusions LPS stimulation alters the miRNA cargo of gingival fibroblast‐derived EVs, enhancing pathways associated with inflammation and cancer progression. These findings suggest a mechanistic role for periodontal EVs in systemic disease pathogenesis, warranting further investigation into their diagnostic and therapeutic potential.https://doi.org/10.1002/cre2.70099 |
| spellingShingle | Daniel Diehl Charlotte Lauren Brauer Hagen S. Bachmann Daniel Pembaur Patrick Philipp Weil Anton Friedmann Extracellular Vesicles Derived From Lipopolysaccharide‐Challenged Gingival Fibroblast Reveal Distinct miRNA Expression Patterns Associated With Reduced Cancer Survival Clinical and Experimental Dental Research |
| title | Extracellular Vesicles Derived From Lipopolysaccharide‐Challenged Gingival Fibroblast Reveal Distinct miRNA Expression Patterns Associated With Reduced Cancer Survival |
| title_full | Extracellular Vesicles Derived From Lipopolysaccharide‐Challenged Gingival Fibroblast Reveal Distinct miRNA Expression Patterns Associated With Reduced Cancer Survival |
| title_fullStr | Extracellular Vesicles Derived From Lipopolysaccharide‐Challenged Gingival Fibroblast Reveal Distinct miRNA Expression Patterns Associated With Reduced Cancer Survival |
| title_full_unstemmed | Extracellular Vesicles Derived From Lipopolysaccharide‐Challenged Gingival Fibroblast Reveal Distinct miRNA Expression Patterns Associated With Reduced Cancer Survival |
| title_short | Extracellular Vesicles Derived From Lipopolysaccharide‐Challenged Gingival Fibroblast Reveal Distinct miRNA Expression Patterns Associated With Reduced Cancer Survival |
| title_sort | extracellular vesicles derived from lipopolysaccharide challenged gingival fibroblast reveal distinct mirna expression patterns associated with reduced cancer survival |
| url | https://doi.org/10.1002/cre2.70099 |
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