Role of connexin 43 in a rat model of periodontitis-induced renal injury

Xin Yu, Fu Ruobing, Xin Xirui, Shang Yaqi, Liu Xinchan, Yu Weixian

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West China Journal of Stomatology ›› 2024, Vol. 42 ›› Issue (3) : 296-303. DOI: 10.7518/hxkq.2024.2023352
Basic Research

Role of connexin 43 in a rat model of periodontitis-induced renal injury

  • Xin Yu1(), Fu Ruobing1, Xin Xirui1, Shang Yaqi1, Liu Xinchan2, Yu Weixian1,3,4()
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Abstract

Objective This study aims to investigate the role of gap junction mediated by connexin 43 (Cx43) in renal injury induced by periodontitis in rats. Methods Twelve SPF-grade Wistar male rats were divided into a control group and a periodontitis group by using a completely random number table method, with six rats in each group. The control group rats were not treated, while the periodontitis group rats were subjected to wire ligation of the neck of their bilateral maxillary first molars to construct a periodontitis model. After 8 weeks of modeling, the rats were examined for clinical indicators of the periodontium. micro-CT scanning of the maxilla reconstructed its 3D structure and analyzed the absorption of alveolar bone. Histopathological changes in periodontal and renal tissues were detected. MitoSOX red reagent was used to determine reactive oxygen species (ROS) content in renal tissues. A biochemical reagent kit was used to detect serum oxidative stress biomarkers. Real-time fluorescent quantitative-polymerase chain reaction (qRT-PCR) was employed to determine Cx43, nuclear factor kappa-B (NF-κB) , interleukin (IL)-1β, IL-6, BCL2-Associated X (Bax), B-lymphomatoma-2 gene (Bcl-2), and Caspase-3 mRNA were determined. Western blot analysis was used to detect Cx43, NF-κB, IL-1β, Bax, Bcl-2 and Caspase-3 protein. Results micro-CT 3D reconstruction showed significant bone resorption of the first molar alveolar bone in the periodontitis group rats and decreased height of the alveolar ridge. The distance from the enamel cementum boundary to the top of the alveolar ridge in the periodontitis group was significantly higher than that inthe control group. The histopathological results showed a large number of inflammatory cells that infiltrated the periodontal tissue of the periodontitis group, and the alveolar bone was significantly absorbed. Rats in the periodontitis group also exhibited mild thickening of the glomerular basement membrane, dilation of the Bowman’s capsule, and destruction of the brush-like edge of the renal tubules in the renal tissue. The MitoSOX red staining results showed a significant increase in ROS content in the renal tissue of the periodontitis group. The biochemical test results showed that the levels of superoxide dismutase and glutathione in the serum of rats with periodontitis decreased, while that of malondialdehyde increased. The results of qRT-PCR and Western blot showed that the expression levels of Cx43, IL-1β, IL-6, Bax, Caspase-3 mRNA and Cx43, IL-1β, NF-κB, Bax, Caspase-3 proteins in the periodontitis group significantly increased compared with those in the control group, while the expression levels of Bcl-2 mRNA and protein decreased. Conclusion Periodontitis may activate NF-κB signaling molecules by upregulating the expression of Cx43 in rat kidney tissues, leading to increased levels of inflammation and apoptosis and ultimately inducing kidney injury.

Key words

periodontitis / renal injury / connexin 43 / rat / apoptosis

CLC number

R781.4

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Xin Yu, Fu Ruobing, Xin Xirui, Shang Yaqi, Liu Xinchan, Yu Weixian. Role of connexin 43 in a rat model of periodontitis-induced renal injury. West China Journal of Stomatology. 2024, 42(3): 296-303 https://doi.org/10.7518/hxkq.2024.2023352

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Funding

International Cooperation Project of Jilin Provincial Department of Science and Technology(20220402-069GH)

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