Abstract
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.
Similar content being viewed by others
References
Llambés F, Arias-Herrera S, Caffesse R (2015) Relationship between diabetes and periodontal infection. World JDiabetes; 6:927–935
Linden GJ, Lyons A, Scannapieco FA (2013) Periodontal systemic associations: review of the evidence. J Clin Periodontol 40(Suppl 14):S8–S19
Chambrone L, Foz AM, Guglielmetti MR, Pannuti CM, Artese HP, Feres M, Romito GA (2013) Periodontitis and chronic kidney disease: a systematic review of the association of diseases and the effect of periodontal treatment on estimated glomerular filtration rate. J Clin Periodontol 40:443–456
Ogrendik M (2013) Rheumatoid arthritis is an autoimmune disease caused by periodontal pathogens. Int J Gen Med 6:383–386
Levey AS, Coresh J (2012) Chronic kidney disease. Lancet 379:165–180
Knotek M, Rogachev B, Wang W, Ecder T, Melnikov V, Gengaro PE, Esson M, Edelstein CL, Dinarello CA, Schrier RW (2001) Endotoxemic renal failure in mice: role of tumor necrosis factor independent of inducible nitric oxide synthase. Kidney Int 59:2243–2249
Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y, Takeda K, Akira S (1999) Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol 162:3749–3752
Darveau RP, Pham TT, Lemley K, Reife RA, Bainbridge BW, Coats SR, Howald WN, Way SS, Hajjar AM (2004) Porphyromonas gingivalis lipopolysaccharide contains multiple lipid A species that functionally interact with both toll-like receptors 2 and 4. Infect Immun 72:5041–5051
Sawa Y, Takata S, Hatakeyama Y, Ishikawa H, Tsuruga E (2014) Expression of toll-like receptor 2 in glomerular endothelial cells and promotion of diabetic nephropathy by Porphyromonas gingivalis lipopolysaccharide. PLoS One 9:e97165
Takahashi K, Mizukami H, Kamata K, Inaba W, Kato N, Hibi C, Yagihashi S (2012) Amelioration of acute kidney injury in lipopolysaccharide-induced systemic inflammatory response syndrome by an aldose reductase inhibitor, fidarestat. PLoS One 7:e30134
Mcmanus JFA, Cason EJ (1950) Carbohydrate histochemistry studied by acetylation techniques; i. periodicacidmethods. J Exp Med 91(6):651–654
Gomori G (1937) Silver impregnation of reticulum in paraffin sections. Am J Pathol 13(6):993–1002.5
Tervaert TW, Mooyaart AL, Amann K, Cohen AH, Cook HT, Drachenberg CB, Franco F, Agnes BF, Mark H, Emile de H, Kensuke J, Laure HN, Jai R, Surya VS, Ingeborg MB, Bruijn Jan A (2010) Pathologic classification of diabetic nephropathy. J Am Soc Nephrol 21:556‒563
Manno C, Strippoli GF, D’Altri C, Torres D, Rossini M, Schena PF (2007) A novel simpler histological classification for renal survival in IgA nephropathy:a retrospective study. Am J Kidney Dis 49:763–775
Ruokonen H, Nylund K, Furuholm J, Meurman JH, Sorsa T, Kotaniemi K, Ortiz F, Heikkinen AM (2017) Oral health and mortality in patients with chronic kidney disease. J Periodontol 88(1):26–33
Larson MA, Wei SH, Weber A, Weber AT, McDonald TL (2003) Induction of human mammary-associated serum amyloid A3 expression by prolactin or lipopolysaccharide. Biochem Biophys Res Commun 301:1030–1037
Seidl SE, Pessolano LG Jr, Bishop CA, Best M, Rich CB, Stone PJ, Schreiber BM (2017) Toll-like receptor 2 activation and serum amyloid A regulate smooth muscle cell extracellular matrix. PLoS One 12(3):e0171711
Sanada Y, Yamamoto T, Satake R, Yamashita A, Kanai S, Kato N, van de Loo FA, Nishimura F, Scherer PE, Yanaka N (2016) Serum amyloid A3 gene expression in adipocytes is an indicator of the interaction with macrophages. Sci Rep 6: 38697
Klein DC, Skjesol A, Kers-Rebel ED, Sherstova T, Sporsheim B, Egeberg KW, Stokke BT, Espevik T, Husebye H (2015) CD14, TLR4 and TRAM show different trafficking dynamics during LPS stimulation. Traffic 16(7):677–690
Wang Y, Jacovetti C, Li B, Siddique T, Xiong X, Yin H, Wang M, Zhao H, Liu JL (2011) Coordinated age-dependent and pancreatic-specific expression of mouse Reg2Reg3α, and Reg3β genes. Growth Factors 29(2–3):72–81
Wang L, Fouts DE, Stärkel P, Hartmann P, Chen P, Llorente C, DePew J, Moncera K, Ho SB, Brenner DA, Hooper LV, Schnabl B (2016) Intestinal REG3 lectins protect against alcoholic steatohepatitis by reducing mucosa-associated microbiota and preventing bacterial translocation. Cell Host Microbe 19(2):227–239
Ferreira L, Quiros Y, Sancho-Martínez SM, García-Sánchez O, Raposo C, López-Novoa JM, González-Buitrago JM, López-Hernández FJ (2011) Urinary levels of regenerating islet-derived protein III beta and gelsolin differentiate gentamicin from cisplatin-induced acute kidney injury in rats. Kidney Int 79:518–528
Onishi M, Yasunaga T, Tanaka H, Nishimune Y, Nozaki M (2004) Gene structure and evolution of testicular haploid germ cell-specific genes, Oxct2a and Oxct2b. Genomics 83:647–657
Marcondes S, Turko IV, Murad F (2001) Nitration of succinyl-CoA:3-oxoacid CoA-transferase in rats after endotoxin administration. Proc Natl Acad Sci USA 98(13):7146–7151
Li K, Wei G, Cao Y, Li D, Li P, Zhang J, Bao H, Chen Y, Fu Y, Sun P, Bai X, Ma X, Lu Z, Liu Z (2017) The identification and distribution of cattle XCR1 and XCL1 among peripheral blood cells: new insights into the design of dendritic cells targeted veterinary vaccine. PLoS One 12:e0170575
Wang CR, Liu MF, Huang YH, Chen HC (2004) Up-regulation of XCR1 expression in rheumatoid joints. Rheumatology 43(5):569–573
Lei Y, Takahama Y (2012) XCL1 and XCR1 in the immune system. Microbes Infect 14(3):262–267
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Harada, F., Uehara, O., Morikawa, T. et al. Effect of systemic administration of lipopolysaccharides derived from Porphyromonas gingivalis on gene expression in mice kidney. Med Mol Morphol 51, 156–165 (2018). https://doi.org/10.1007/s00795-018-0181-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00795-018-0181-3