Expression of toll-like receptor 2 in glomerular endothelial cells and promotion of diabetic nephropathy by Porphyromonas gingivalis lipopolysaccharide.
The toll-like receptor (TLR) has been suggested as a candidate cause for diabetic nephropathy. Recently, we have reported the TLR4 expression in diabetic mouse glomerular endothelium. The study here investigates the effects of the periodontal pathogen Porphyromonas gingivalis lipopolysaccharide (LPS) which is a ligand for TLR2 and TLR4 in diabetic nephropathy. In laser-scanning microscopy of glomeruli of streptozotocin- and a high fat diet feed-induced type I and type II diabetic mice, TLR2 localized on the glomerular endothelium and proximal tubule epithelium. The TLR2 mRNA was detected in diabetic mouse glomeruli by in situ hybridization and in real-time PCR of the renal cortex, the TLR2 mRNA amounts were larger in diabetic mice than in non-diabetic mice. All diabetic mice subjected to repeated LPS administrations died within the survival period of all of the diabetic mice not administered LPS and of all of the non-diabetic LPS-administered mice. The LPS administration promoted the production of urinary protein, the accumulation of type I collagen in the glomeruli, and the increases in IL-6, TNF-α, and TGF-β in the renal cortex of the glomeruli of the diabetic mice. It is thought that blood TLR ligands like Porphyromonas gingivalis LPS induce the glomerular endothelium to produce cytokines which aid glomerulosclerosis. Periodontitis may promote diabetic nephropathy.
Department of Morphological Biology, Fukuoka Dental College, Fukuoka, Japan.
Yoshihiko
Y
Sawa
Department of Oral Growth & Development, Fukuoka Dental College, Fukuoka, Japan.
Shunsuke
S
Takata
Department of Morphological Biology, Fukuoka Dental College, Fukuoka, Japan.
Yuji
Y
Hatakeyama
Department of Oral Growth & Development, Fukuoka Dental College, Fukuoka, Japan.
Hiroyuki
H
Ishikawa
Department of Morphological Biology, Fukuoka Dental College, Fukuoka, Japan.
Eichi
E
Tsuruga
D000704:Analysis of Variance; D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000139:chemically induced*; D042783:Endothelial Cells / Q000378:metabolism*; D017403:In Situ Hybridization; D015850:Interleukin-6 / Q000378:metabolism; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D016966:Porphyromonas gingivalis / Q000737:chemistry*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D024042:Collagen Type I; D015850:Interleukin-6; D008070:Lipopolysaccharides; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha