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

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.

journal_name

Diabetol Metab Syndr

journal_title

Diabetology & metabolic syndrome

authors

Kajiwara K,Takata S,To TT,Takara K,Hatakeyama Y,Tamaoki S,Darveau RP,Ishikawa H,Sawa Y

doi

10.1186/s13098-017-0271-8

subject

Has Abstract

pub_date

2017-09-22 00:00:00

pages

issn

1758-5996

pii

271

journal_volume

pub_type

杂志文章

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