Harada Fumiya, Uehara Osamu, Morikawa Tetsuro, Hiraki Daichi, Onishi Aya, Toraya Seiko, Adhikari Bhoj Raj, Takai Rie, Yoshida Koki, Sato Jun, Nishimura Michiko, Chiba Itsuo, Wu Ching Zong, Abiko Yoshihiro
Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan.
School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
Med Mol Morphol. 2018 Sep;51(3):156-165. doi: 10.1007/s00795-018-0181-3. Epub 2018 Jan 31.
Although an association between periodontitis and chronic kidney disease (CKD) has been suggested, the mechanism involved remains unclear. Herein, we examined the global gene expression profile in a mouse model that showed no acute inflammation in the kidney following stimulation with lipopolysaccharides (LPS) derived from Porphyromonas gingivalis (PG-LPS). The mice were injected with PG-LPS at a concentration of 5 mg/kg intraperitoneally, every 3 days, for 1 month. Microarray analysis was used to identify 10 genes with the highest expression levels in the kidney stimulated with PG-LPS. Among them, the functions of five genes (Saa3, Ticam2, Reg3b, Ocxt2a, and Xcr1) were known. The upregulation of these genes was confirmed by quantitative polymerase chain reaction assay. Furthermore, we examined whether the expression of these upregulated genes were altered in endothelial cells derived from the kidney, in vitro. The mRNA expression levels of all five genes were significantly higher in the experimental group than in the controls (no LPS stimulation; *p < 0.05). In conclusion, the responses noted in the kidney may have arisen mainly from the endothelial cells. Moreover, upregulation of the expression levels of Saa3, Ticam2, Reg3b, Ocxt2a, and Xcr1 may be associated with the pathogenesis of CKD.
虽然已有研究表明牙周炎与慢性肾脏病(CKD)之间存在关联,但其潜在机制仍不明确。在此,我们检测了一种小鼠模型的全基因组表达谱,该模型在用牙龈卟啉单胞菌来源的脂多糖(PG-LPS)刺激后,肾脏未出现急性炎症反应。以5mg/kg的浓度,每3天给小鼠腹腔注射PG-LPS,持续1个月。利用基因芯片分析确定了在PG-LPS刺激的肾脏中表达水平最高的10个基因。其中,5个基因(Saa3、Ticam2、Reg3b、Ocxt2a和Xcr1)的功能已知。通过定量聚合酶链反应检测证实了这些基因的上调。此外,我们还在体外检测了这些上调基因在源自肾脏的内皮细胞中的表达是否发生改变。实验组中所有5个基因的mRNA表达水平均显著高于对照组(未进行LPS刺激;*p < 0.05)。总之,肾脏中观察到的反应可能主要源于内皮细胞。此外,Saa3、Ticam2、Reg3b、Ocxt2a和Xcr1表达水平的上调可能与CKD的发病机制有关。