The promotion of nephropathy by Porphyromonas gingivalis lipopolysaccharide via toll-like receptors

Koichiro Kajiwara, Shunsuke Takata, Thao T. To, Kenyo Takara, Yuji Hatakeyama, Sachio Tamaoki, Richard Peters Darveau, Hiroyuki Ishikawa, Yoshihiko Sawa

Research output: Contribution to journalArticle

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Abstract

Background: Recently, we reported that toll-like receptor (TLR)2 and TLR4 localized on the glomerular endothelium in the glomeruli of streptozotocin (STZ)-induced type 1 diabetic mice and high fat diet feed-induced type 2 diabetic mice, and that periodontal pathogen Porphyromonas gingivalis LPS (Pg-LPS) administration lowered the survival rate of diabetic mice. The present study aims to examine the effect of TLR4 blocking on the suppression of Pg-LPS-induced diabetic nephropathy. Methods: The survival rate and morphological/biochemical features for streptozotocin-induced diabetic mice with Pg-LPS and TLR4 blocker eritoran administration were investigated by reporter gene assay, urine and blood analysis, immunohistochemistry, and real time-PCR. Results and Conclusions: All of the diabetic mice administered Pg-LPS were euthanized within the survival period of almost all of the diabetic mice. The blood urea nitrogen and creatinine, expression of TLR2 and TGF-b, and type 1 collagen accumulation, in the diabetic mice increased significantly with the Pg-LPS administration. In spite of the limited TLR4 activation with Pg-LPS, the TLR4 blocker eritoran decreased blood urea nitrogen and creatinine, and raised the survival rate of the Pg-LPS-administered diabetic mice slightly. The high expression levels of TLR2, TGF-b, and type 1 collagen in Pg-LPS-administered diabetic mice decreased with eritoran. Nuclear STAT3 which enhances TLR2 expression was detected in the TLR2-expressing glomeruli of diabetic mice. The TLR2 and STAT3 gene expression increased by the Pg-LPS administration but decreased with eritoran. These may suggest that Pg-LPS-induced diabetic nephropathy is mainly dependent on TLR2 signaling on glomerular endothelial cells, and that TLR4 blocker eritoran may play a role to slow the progress of diabetic nephropathy.

Original languageEnglish
Article number73
JournalDiabetology and Metabolic Syndrome
Volume9
Issue number1
DOIs
Publication statusPublished - Sep 22 2017

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Porphyromonas gingivalis
Toll-Like Receptors
Lipopolysaccharides
Diabetic Nephropathies
Blood Urea Nitrogen
Streptozocin
Collagen Type I
Creatinine
Toll-Like Receptor 2
High Fat Diet
Reporter Genes
Endothelium
Real-Time Polymerase Chain Reaction
Endothelial Cells
Immunohistochemistry
eritoran
Urine
Gene Expression

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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The promotion of nephropathy by Porphyromonas gingivalis lipopolysaccharide via toll-like receptors. / Kajiwara, Koichiro; Takata, Shunsuke; To, Thao T.; Takara, Kenyo; Hatakeyama, Yuji; Tamaoki, Sachio; Darveau, Richard Peters; Ishikawa, Hiroyuki; Sawa, Yoshihiko.

In: Diabetology and Metabolic Syndrome, Vol. 9, No. 1, 73, 22.09.2017.

Research output: Contribution to journalArticle

Kajiwara, K, Takata, S, To, TT, Takara, K, Hatakeyama, Y, Tamaoki, S, Darveau, RP, Ishikawa, H & Sawa, Y 2017, 'The promotion of nephropathy by Porphyromonas gingivalis lipopolysaccharide via toll-like receptors', Diabetology and Metabolic Syndrome, vol. 9, no. 1, 73. https://doi.org/10.1186/s13098-017-0271-8
Kajiwara, Koichiro ; Takata, Shunsuke ; To, Thao T. ; Takara, Kenyo ; Hatakeyama, Yuji ; Tamaoki, Sachio ; Darveau, Richard Peters ; Ishikawa, Hiroyuki ; Sawa, Yoshihiko. / The promotion of nephropathy by Porphyromonas gingivalis lipopolysaccharide via toll-like receptors. In: Diabetology and Metabolic Syndrome. 2017 ; Vol. 9, No. 1.
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AU - Hatakeyama, Yuji

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