The promotion of nephropathy by Porphyromonas gingivalis lipopolysaccharide via toll-like receptors.
The promotion of nephropathy by Porphyromonas gingivalis lipopolysaccharide via toll-like receptors.
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牙龈卟啉单胞菌脂多糖通过 Toll 样受体促进肾病。
DOI：
10.1186/s13098-017-0271-8
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发表时间：
2017
影响因子：
4.8
通讯作者：
Sawa Y
中科院分区：
文献类型：
--
作者：
Kajiwara K;Takata S;To TT;Takara K;Hatakeyama Y;Tamaoki S;Darveau RP;Ishikawa H;Sawa Y
最近，我们报道了Toll样受体（TLR）2和TLR 4定位于链脲佐菌素（STZ）诱导的1型糖尿病小鼠和高脂饮食诱导的2型糖尿病小鼠的肾小球内皮细胞，牙周病原体牙龈卟啉单胞菌LPS（Pg-LPS）给药降低糖尿病小鼠的存活率。本研究旨在检测TLR 4阻断对Pg-LPS诱导的糖尿病肾病的抑制作用。通过报告基因检测、尿和血液分析、免疫组化和真实的时间PCR检测链脲佐菌素诱导的糖尿病小鼠在Pg-LPS和TLR 4阻断剂eritoran干预下的存活率和形态学/生化特征。在几乎所有糖尿病小鼠的存活期内，对所有施用Pg-LPS的糖尿病小鼠实施安乐死。Pg-LPS组小鼠血尿素氮、肌酐、TLR 2、TGF-β表达及1型胶原积累均显著增加。尽管Pg-LPS对TLR 4的激活作用有限，但TLR 4阻断剂eritoran可降低血尿素氮和肌酐，并略微提高Pg-LPS给药的糖尿病小鼠的存活率。eritoran降低了Pg-LPS给药的糖尿病小鼠中TLR 2、TGF-β和1型胶原的高表达水平。在糖尿病小鼠表达TLR 2的肾小球中检测到核STAT 3，其增强TLR 2表达。TLR 2和STAT 3基因的表达增加Pg-LPS的管理，但与eritoran下降。提示Pg-LPS诱导的糖尿病肾病主要依赖于肾小球内皮细胞上的TLR 2信号，TLR 4阻断剂eritoran可能在延缓糖尿病肾病的进展中发挥作用。
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. 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. 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.
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影响因子：
3.4
作者：
Coats SR;Jones JW;Do CT;Braham PH;Bainbridge BW;To TT;Goodlett DR;Ernst RK;Darveau RP
通讯作者：
Darveau RP
ERK/MAPK 和 TGF-Beta/Smad 信号通路在血糖波动加速的糖尿病小鼠肾纤维化中发挥作用
影响因子：
4.3
作者：
Cheng X;Gao W;Dang Y;Liu X;Li Y;Peng X;Ye X
通讯作者：
Ye X
影响因子：
3.4
作者：
Chen, Casey;Coats, Stephen R.;Darveau, Richard P.
通讯作者：
Darveau, Richard P.
影响因子：
4.2
作者：
Li, Fanglin;Yang, Niansheng;Yu, Xueqing
通讯作者：
Yu, Xueqing
影响因子：
7.7
作者：
Huang C;Shen S;Ma Q;Chen J;Gill A;Pollock CA;Chen XM
通讯作者：
Chen XM