Porphyromonas gingivalis induces chronic kidney disease through
crosstalk between the NF‑κB/NLRP3 pathway and ferroptosis in GMCs
Xue Li1,2,3, Chao Yao1,2,3, Dongmei
Lan1,2,3, Yan Wang1,2,3*, Shengcai
Qi1,2,3*
1. Department of Prothodontics, Shanghai Stomatological Hospital, Fudan
University
2. Shanghai Key Laboratory of Craniomaxillofacial Development and
Diseases, Fudan University
3. Medical College, Anhui University of Science and Technology, Huainan,
China
Abstract: Porphyromonas gingivalis (P.g) 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.g in CKD pathogenesis are
unclear. In this study, an animal model of oral P.gadministration and glomerular mesangial cells (GMCs) cocultured with
M1-polarized macrophages and P.g supernatant were constructed. We
found that oral P.g administration induced CKD in mice.P.g supernatant induced m! 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 . In
conclusion, we demonstrated that P.g induced CKD in mice by
triggering crosstalk between the NF‑κB/NLRP3 pathway and ferroptosis in
GMCs. Overall, our study suggests 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.
Key words: Porphyromonas gingivalis ; Chronic kidney
disease; Glomerular mesangial cells; Macrophages; NF‑κB/NLRP3 pathway;
Ferroptosis