Wei Wei, Jing Sun, Zhaoxin Ji, Jiangqi Hu, Qingsong Jiang
{"title":"在牙周炎相关急性肾损伤中,Gingipain 和 oncostatin M 能协同破坏肾脏紧密连接。","authors":"Wei Wei, Jing Sun, Zhaoxin Ji, Jiangqi Hu, Qingsong Jiang","doi":"10.1002/JPER.24-0007","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Acute 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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>This study explored the effects of <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>) 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 <i>P. gingivalis</i> 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 <i>P. gingivalis</i> 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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Periodontitis worsened AKI, linked to <i>P. gingivalis</i> infection and renal TJ disruption in the kidney. <i>P. gingivalis</i> 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.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Our study enhances the understanding of the interplay between periodontitis and AKI, highlighting the harmful impact of <i>P. gingivalis</i> in AKI.</p>\n </section>\n </div>","PeriodicalId":16716,"journal":{"name":"Journal of periodontology","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/JPER.24-0007","citationCount":"0","resultStr":"{\"title\":\"Gingipain and oncostatin M synergistically disrupt kidney tight junctions in periodontitis-associated acute kidney injury\",\"authors\":\"Wei Wei, Jing Sun, Zhaoxin Ji, Jiangqi Hu, Qingsong Jiang\",\"doi\":\"10.1002/JPER.24-0007\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Acute 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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>This study explored the effects of <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>) 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 <i>P. gingivalis</i> 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 <i>P. gingivalis</i> 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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Periodontitis worsened AKI, linked to <i>P. gingivalis</i> infection and renal TJ disruption in the kidney. <i>P. gingivalis</i> 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. 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引用次数: 0
摘要
背景:急性肾损伤(AKI)的特点是肾功能急剧下降。牙周炎是一种慢性口腔炎症性疾病,越来越多地与肾功能障碍相关。尽管牙周炎被认为是造成肾损伤的一个因素,但它与急性肾损伤的关联机制仍不清楚:本研究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式反应(qRT-PCR)和 PCR 检测牙龈脓疱病,同时使用转录组测序、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的感染倍数暴露于牙龈脓疱疮菌48小时,并受到gingipain或oncostatin M(OSM)的抑制。使用 qRT-PCR、跨上皮电阻和细胞计数试剂盒-8 检测法量化紧密连接(TJ)的破坏情况:结果:牙周炎加重了 AKI,这与牙龈脓胞感染和肾脏 TJ 破坏有关。牙龈脓疱疮感染激活了 OSM 的表达,而 OSM 的表达与 gingipain 呈正相关。值得注意的是,OSM和gingipain可能会共同导致肾脏TJ受损,同时降低TJ蛋白的表达。抑制gingipain的活性可作为一种保护性策略,防止TJ被破坏以及随之而来的牙周炎导致的AKI恶化:我们的研究加深了人们对牙周炎与 AKI 之间相互作用的理解,突出了牙龈脓疱病在 AKI 中的有害影响。
Gingipain and oncostatin M synergistically disrupt kidney tight junctions in periodontitis-associated acute kidney injury
Background
Acute 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.
Methods
This 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.
Results
Periodontitis 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.
Conclusions
Our study enhances the understanding of the interplay between periodontitis and AKI, highlighting the harmful impact of P. gingivalis in AKI.