State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, China.
Ningbo Stomatological Hospital, China.
FEBS Open Bio. 2021 Mar;11(3):880-889. doi: 10.1002/2211-5463.13081. Epub 2021 Feb 19.
Periodontitis is an autoimmune disease of periodontal tissues initiated by plaque. It is known that there is a close connection between periodontitis and CKD with hypertension, but the underlying mechanisms are unknown. STAT1 has been reported to play a regulatory role in hypertension and chronic kidney disease (CKD). Here, we investigated whether STAT1 regulates periodontitis-mediated aggravation of kidney injury with accompanying hypertension. A hypertensive renal injury mouse model was established with Nos3 knockout mice, and a periodontitis model was established by implantation with the oral bacteria Porphyromonas gingivalis. The mice were intraperitoneally injected with a STAT1 inhibitor. Periodontitis aggravated kidney injury in hypertensive mice, and upregulation of STAT1 was observed when both periodontitis and hypertension were present; furthermore, STAT1 inhibitor moderated this effect. Moreover, we observed that periodontitis promoted the upregulation of inflammatory and fibrosis gene expression in the kidneys of hypertensive mice. In addition, STAT1 inhibition decreased the expression of pro-inflammatory and pro-fibrotic cytokines in the kidney lesion area. Periodontitis augmented the expression of inflammatory and fibrosis genes by upregulating the expression of STAT1, thereby aggravating kidney injury in the hypertensive mouse model.
牙周炎是一种由菌斑引发的牙周组织自身免疫性疾病。已知牙周炎与高血压性慢性肾脏病（CKD）密切相关，但具体机制尚不清楚。STAT1 已被报道在高血压和慢性肾脏病（CKD）中发挥调节作用。在这里，我们研究了 STAT1 是否调节牙周炎介导的高血压伴发的肾损伤加重。利用 Nos3 基因敲除小鼠建立高血压肾损伤小鼠模型，并通过植入口腔细菌牙龈卟啉单胞菌建立牙周炎模型。然后对小鼠进行 STAT1 抑制剂腹腔注射。牙周炎加重了高血压小鼠的肾损伤，当同时存在牙周炎和高血压时，观察到 STAT1 上调；此外，STAT1 抑制剂缓和了这一作用。此外，我们观察到牙周炎促进了高血压小鼠肾脏中炎症和纤维化基因表达的上调。此外，STAT1 抑制减少了肾病变区域促炎和促纤维化细胞因子的表达。牙周炎通过上调 STAT1 的表达来增加炎症和纤维化基因的表达，从而加重高血压小鼠模型的肾损伤。
