Porphyromonas gingivalis Induces Chronic Kidney Disease through Crosstalk between the NF-κB/NLRP3 Pathway and Ferroptosis in GMCs

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外文摘要：Objective:Porphyromonas gingivalis(P.gingivalis)is a gram-negative bacterium found in the human oral cavity and is a recognized pathogenic bacterium associated with chronic periodontitis and systemic diseases,including chronic kidney disease(CKD),but the roles and molecular mechanism of P.gingivalis in CKD pathogenesis are unclear.Methods:In this study,an animal model of oral P.gingivalis administration and glomerular mesangial cells(GMCs)cocultured with Ml-polarized macrophages and P.gingivalis supernatant were constructed.After seven weeks of P.gingivalis gavaged,peripheral blood was collected to detect the changes in renal function.By collecting the teeth and kidneys of mice,H&E staining and IHC were used to analyze the expression of periodontal inflammatory factors in mice,PAS staining was used to analyze glomerular lesions.The supernatant of macrophages was treated with 5％P.gingivalis supernatant.H&E staining,IHC,Western blot and RT-PCR were applied to analyze renal inflammatory factors,macrophage Ml polarization,NF-κB,NLRP3 and ferroptosis changes in vitro.Results:We found that oral P.gingivalis administration induced CKD in mice.P.gingivalis supernatant induced macrophage polarization and inflammatory factor upregulation,which triggered the activation of the NF-κB/NLRP3 pathway and ferroptosis in GMCs.By inhibiting the NF-κB/NLRP3 pathway and ferroptosis in GMCs,cell viability and the inflammatory response were partially alleviated in vitro.Conclusion:We demonstrated that P.gingivalis induced CKD in mice by triggering crosstalk between the NF κB/NLRP3 pathway and ferroptosis in GMCs.Overall,our study suggested that periodontitis can promote the pathogenesis of CKD in mice,which provides evidence of the importance of periodontitis therapy in the prevention and treatment of CKD.

外文关键词：

Porphyromonas gingivalischronic kidney diseaseglomerular mesangial cellsmacrophagesNF-κB/NLRP3 pathwayferroptosis

作者：

Xue LI、Chao YAO、Dong-mei LAN、Yan WANG、Sheng-cai QI

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作者单位：

Medical College,Anhui University of Science and Technology,Huainan 232007,China

Department of Oral Prosthodontics,Shanghai Stomatological Hospital,Fudan University,Shanghai 200001,China

Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases,Shanghai Stomatological Hospital & School of Stomatology Fudan University Shanghai 200002,China

Department of Orthodontics,Shanghai Stomatological Hospital & School of Stomatology,Fudan University,Shanghai 200433,China

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出版年：

2024

DOI：

10.1007/s11596-024-2923-x

当代医学科学(英文)

华中科技大学同济医学院

当代医学科学(英文)

影响因子：0.748

ISSN：2096-5230

年,卷(期)：2024.44(5)