Role of ferroptosis in Porphyromonas gingivalis-induced impairment of epithelial junction

ABSTRACTObjectives This study aims to clarify the effect of ferroptosis by P. gingivalis on periodontal epithelium impairment and potential mechanisms.Materials and methods The expression of epithelial junction proteins (CDH1, OCLN, ZO-1), FTL and GPX4 in healthy and periodontitis tissues was analyz...

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Main Authors: Xiaoting Shi, Jinwen Liu, Ze Lu, Jiabo Li, Shuwei Zhang, Qian Li, Fengxue Geng, Yaping Pan
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Journal of Oral Microbiology
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/20002297.2024.2334578
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author Xiaoting Shi
Jinwen Liu
Ze Lu
Jiabo Li
Shuwei Zhang
Qian Li
Fengxue Geng
Yaping Pan
author_facet Xiaoting Shi
Jinwen Liu
Ze Lu
Jiabo Li
Shuwei Zhang
Qian Li
Fengxue Geng
Yaping Pan
author_sort Xiaoting Shi
collection DOAJ
description ABSTRACTObjectives This study aims to clarify the effect of ferroptosis by P. gingivalis on periodontal epithelium impairment and potential mechanisms.Materials and methods The expression of epithelial junction proteins (CDH1, OCLN, ZO-1), FTL and GPX4 in healthy and periodontitis tissues was analyzed using bioinformatics analysis and validated in vivo. An in vitro model was constructed to evaluate ferroptosis by mitochondria morphology, content of iron and GSH, and level of lipid peroxidation, FTL, GPX4 and SLC7A11. The iron concentration was changed with iron chelator DFO and iron supplementation FAC. The epithelial impairment was assessed by protein expression. To investigate the mechanism, si-MYB (a negative transcription factor of SLC7A11) and GPX4 inhibitor RSL3 were employed.Results CDH1, OCLN, ZO-1 and GPX4 expression was decreased, while FTL expression was elevated in periodontitis tissues. Infected cells showed ferroptosis change of the mitochondria with higher level of lipid peroxidation, iron, FTL and lower level of GPX4, GSH, SLC7A11. FAC augmented ferroptosis and weakened epithelial junction, while DFO exhibited a counteractive effect. Silencing MYB rescued SLC7A11, GPX4 and epithelial junction proteins, which was hindered by RSL3.Conclusions Our study demonstrated that P. gingivalis weakened the oral epithelial barrier by causing ferroptosis via inhibiting SLC7A11/GSH/GPX4 axis.
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spelling doaj.art-fd3759e0b4e64222966479862f14dacc2024-04-16T20:33:16ZengTaylor & Francis GroupJournal of Oral Microbiology2000-22972024-12-0116110.1080/20002297.2024.2334578Role of ferroptosis in Porphyromonas gingivalis-induced impairment of epithelial junctionXiaoting Shi0Jinwen Liu1Ze Lu2Jiabo Li3Shuwei Zhang4Qian Li5Fengxue Geng6Yaping Pan7Department of Periodontics, Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University, Shenyang, ChinaDepartment of Periodontics, Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University, Shenyang, ChinaDepartment of Periodontics, Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University, Shenyang, ChinaDepartment of Periodontics, Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University, Shenyang, ChinaDepartment of Periodontics, Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University, Shenyang, ChinaDepartment of Periodontics, Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University, Shenyang, ChinaDepartment of Periodontics, Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University, Shenyang, ChinaDepartment of Periodontics, Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University, Shenyang, ChinaABSTRACTObjectives This study aims to clarify the effect of ferroptosis by P. gingivalis on periodontal epithelium impairment and potential mechanisms.Materials and methods The expression of epithelial junction proteins (CDH1, OCLN, ZO-1), FTL and GPX4 in healthy and periodontitis tissues was analyzed using bioinformatics analysis and validated in vivo. An in vitro model was constructed to evaluate ferroptosis by mitochondria morphology, content of iron and GSH, and level of lipid peroxidation, FTL, GPX4 and SLC7A11. The iron concentration was changed with iron chelator DFO and iron supplementation FAC. The epithelial impairment was assessed by protein expression. To investigate the mechanism, si-MYB (a negative transcription factor of SLC7A11) and GPX4 inhibitor RSL3 were employed.Results CDH1, OCLN, ZO-1 and GPX4 expression was decreased, while FTL expression was elevated in periodontitis tissues. Infected cells showed ferroptosis change of the mitochondria with higher level of lipid peroxidation, iron, FTL and lower level of GPX4, GSH, SLC7A11. FAC augmented ferroptosis and weakened epithelial junction, while DFO exhibited a counteractive effect. Silencing MYB rescued SLC7A11, GPX4 and epithelial junction proteins, which was hindered by RSL3.Conclusions Our study demonstrated that P. gingivalis weakened the oral epithelial barrier by causing ferroptosis via inhibiting SLC7A11/GSH/GPX4 axis.https://www.tandfonline.com/doi/10.1080/20002297.2024.2334578Porphyromonas gingivalisperiodontitisferroptosisepithelial junctioniron overload
spellingShingle Xiaoting Shi
Jinwen Liu
Ze Lu
Jiabo Li
Shuwei Zhang
Qian Li
Fengxue Geng
Yaping Pan
Role of ferroptosis in Porphyromonas gingivalis-induced impairment of epithelial junction
Journal of Oral Microbiology
Porphyromonas gingivalis
periodontitis
ferroptosis
epithelial junction
iron overload
title Role of ferroptosis in Porphyromonas gingivalis-induced impairment of epithelial junction
title_full Role of ferroptosis in Porphyromonas gingivalis-induced impairment of epithelial junction
title_fullStr Role of ferroptosis in Porphyromonas gingivalis-induced impairment of epithelial junction
title_full_unstemmed Role of ferroptosis in Porphyromonas gingivalis-induced impairment of epithelial junction
title_short Role of ferroptosis in Porphyromonas gingivalis-induced impairment of epithelial junction
title_sort role of ferroptosis in porphyromonas gingivalis induced impairment of epithelial junction
topic Porphyromonas gingivalis
periodontitis
ferroptosis
epithelial junction
iron overload
url https://www.tandfonline.com/doi/10.1080/20002297.2024.2334578
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