BackgroundAcute kidney injury (AKI) is characterized by rapid renal decline. Periodontitis, a chronic oral inflammatory disease, is increasingly associated with renal dysfunction. Although periodontitis is recognized as a contributor to kidney damage, the mechanisms linking it to AKI remain unclear.MethodsThis study explored the effects of Porphyromonas gingivalis (P. gingivalis) W83‐infected periodontitis on AKI in C57BL/6J mice, using ischemia‐reperfusion injury 55 days post‐infection. Gingipain inhibitors, KYT‐1 and KYT‐36, were applied. Detection of P. gingivalis was performed using quantitative real‐time polymerase chain reaction (qRT‐PCR) and PCR, while transcriptome sequencing, qRT‐PCR, immunohistochemistry, and immunofluorescence staining assessed renal damage. In vitro, HK‐2 cells were exposed to P. gingivalis at a multiplicity of infection of 10 for 48 h, with inhibition by gingipain or oncostatin M (OSM). Disruption of tight junctions (TJs) was quantified using qRT‐PCR, transepithelial electrical resistance, and cell counting kit‐8 assays.ResultsPeriodontitis worsened AKI, linked to P. gingivalis infection and renal TJ disruption in the kidney. P. gingivalis infection activated OSM expression, which correlated positively with gingipain. Significantly, OSM and gingipain might collaboratively contribute to the damage of renal TJs, with the reduced expression of TJ proteins. Suppressing gingipain activity presented itself as a protective strategy against the destruction of TJs and the attendant worsening of AKI due to periodontitis.ConclusionsOur study enhances the understanding of the interplay between periodontitis and AKI, highlighting the harmful impact of P. gingivalis in AKI.

中文翻译：

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牙龈蛋白酶和抑瘤素 M 协同破坏牙周炎相关急性肾损伤的肾脏紧密连接


背景急性肾损伤 （AKI） 的特征是肾功能迅速下降。牙周炎是一种慢性口腔炎症性疾病，与肾功能障碍的关系越来越密切。尽管牙周炎被认为是导致肾脏损伤的原因，但将其与 AKI 联系起来的机制仍不清楚。方法本研究利用感染后 55 天的缺血再灌注损伤，探讨了牙龈卟啉单胞菌 （P. gingivalis） W83 感染的牙周炎对 C57BL/6J 小鼠 AKI 的影响。应用牙龈蛋白酶抑制剂 KYT-1 和 KYT-36。使用定量实时聚合酶链反应 （qRT-PCR） 和 PCR 检测牙龈卟啉单胞菌，同时转录组测序、qRT-PCR、免疫组织化学和免疫荧光染色评估肾损伤。在体外，HK-2 细胞以 10 次感染的多重性暴露于牙龈卟啉单胞菌 48 小时，并受到牙龈蛋白酶或抑瘤素 M （OSM） 的抑制。使用 qRT-PCR、跨上皮电阻和细胞计数试剂盒-8 测定对紧密连接 （TJ） 的破坏进行定量。结果牙周炎使 AKI 恶化，与牙龈卟啉单胞菌感染和肾脏 TJ 破坏有关。P. gingivalis 感染激活了 OSM 表达，这与牙龈蛋白酶呈正相关。值得注意的是，OSM 和牙龈蛋白酶可能共同导致肾 TJ 损伤，降低 TJ 蛋白的表达。抑制牙龈蛋白酶活性是一种保护策略，可防止 TJ 的破坏和随之而来的牙周炎引起的 AKI 恶化。结论我们的研究增强了对牙周炎与 AKI 之间相互作用的理解，突出了牙龈卟啉单胞菌对 AKI 的有害影响。