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 P.; Ishikawa, Hiroyuki; Sawa, Yoshihiko

doi:10.1186/s13098-017-0271-8

Cited by 12 publications

(31 citation statements)

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“…The health status and humane endpoints of the mice were assessed daily and mice which had lost the ability to ambulate and to access food or water were euthanized by induction anesthesia followed by cervical dislocation and intraperitoneal injections with sodium pentobarbital. The experimental drug administration to the mice were performed under anesthesia according to the method described elsewhere (23). All mice in the experimental groups were maintained till euthanization.…”

Section: Animalsmentioning

confidence: 99%

“…The STZ-injected ICR mice were used as a diabetic model and STZ and P. gingivalis LPS injected ICR mice were used as a diabetic nephropathy model (23). Following procedures described elsewhere (23).…”

Section: Animalsmentioning

confidence: 99%

“…The present study performed the investigation by immunohistochemistry following the method described elsewhere (23). Brie y, frozen mouse kidney tissue sections were xed in 100% methanol and treated with primary antibodies: hamster monoclonal anti-mouse podoplanin clone 8.8.1 (BioLegend Inc., San Diego, CA) as a podocyte marker, rat monoclonal anti-mouse VCAM-1 (R&D Systems Inc., Minneapolis, MN), rat monoclonal anti-mouse E-selectin (R&D Systems), rabbit polyclonal anti-mouse FDF23 (Abcam plc., Cambridge, UK), rabbit polyclonal AGE2 (Abcam), and rat polyclonal anti-mouse CD11b clone M1/70 (macrophage-1, Mac-1a; BD Biosciences, San Jose, CA).…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…In diabetic mice P. gingivalis LPS promoted the production of urinary protein and glomerulosclerosis with the accumulation of type 1 collagen and in ammatory cytokines in glomeruli. Further, the progress of diabetic nephropathy was suppressed in TLR blockage Eritoran-administered diabetic mice, where the albuminuria and glomerular hypertrophy were less pronounced than in diabetic mice not administered Eritoran (23). Severe periodontitis causes bacteremia and microorganisms of the oral cavity to enter the kidneys through the systemic circulation, and it appears that P. gingivalis LPS accumulated in glomeruli induce chronic renal in ammation as a result of the in ammatory leukocyte migration.…”

Section: Introductionmentioning

confidence: 97%

“…We recently reported that the glomerular endothelium of streptozotocin (STZ)-induced diabetic mice expresses TLR2 and TLR4, and that all diabetic mice subjected to repeated P. gingivalis LPS administrations euthanized within the health survival period of all of diabetic mice not administered LPS and LPS-administered non-diabetic mice (21)(22)(23). In diabetic mice P. gingivalis LPS promoted the production of urinary protein and glomerulosclerosis with the accumulation of type 1 collagen and in ammatory cytokines in glomeruli.…”

Section: Introductionmentioning

confidence: 99%

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Induction of leukocyte adhesion molecules and renal physiologically active molecules in Porphyromonas gingivalis lipopolysaccharide-induced diabetic nephropathy

Kajiwara¹,

Sawa²,

Fujita³

et al. 2020

Preprint

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Background We recently reported that the glomerular endothelium expresses toll-like receptor (TLR)2 and TLR4 in diabetic environments and established that the TLR2 ligand Porphyromonas (P.) gingivalis lipopolysaccharides (LPS) induces nephropathy in diabetic mice. It is thought that P. gingivalis LPS promotes the chronic inflammation with the overexpression of leukocyte adhesion molecules and renal-specific metabolic enzymes by the recognition of P. gingivalis LPS via TLR in the diabetic kidneys. The present study aims to examine the expression of leukocyte adhesion molecules and renal metabolic factors in mouse kidneys with periodontal pathogen P. gingivalis LPS-induced diabetic nephropathy that was recently established. Methods The immunohistochemical investigation was performed on mouse kidney with P. gingivalis LPS-induced diabetic nephropathy model with glomerulosclerosis in glomeruli. Results There were no vessels which expressed vascular cell adhesion molecule-1 (VCAM-1), E-selectin, or fibroblast growth factor (FGF) 23 in diabetic mice, or in healthy mice administered P. gingivalis LPS. However, in diabetic mouse kidneys with P. gingivalis LPS-induced nephropathy the expression of VCAM-1 and the accumulation of FGF23 were established in renal tubules and glomeruli, and the expression of E-selectin was established in renal parenchyma and glomeruli. The angiotensin-converting enzyme 2 (ACE2) was detected in the proximal tubules but not in other regions including not in distal tubules of diabetic mice without LPS, and not in healthy mice administered P. gingivalis LPS. In diabetic mouse kidneys with P. gingivalis LPS-induced nephropathy ACE2 was detected both in renal tubules as well as in glomeruli. The macrophage-1 (Mac-1) and podoplanin-positive cells increased in the renal parenchyma with diabetic condition and there was accumulation in P. gingivalis LPS-induced diabetic nephropathy. As the expression of VCAM-1 and E-selectin is upregulated in glomeruli, tubules, and intertubular capillaries, it is thought that the inflammatory infiltration of the monocyte-macrophage lineage promoted in kidneys with P. gingivalis LPS-induced the diabetic nephropathy. Conclusions P. gingivalis LPS may progressively accelerate the development of the renal inflammatory environment in LPS-accumulated glomeruli with the macrophage infiltration via the renal expression of VCAM-1 and E-selectin, and with ACE2 overexpression and FGF23 accumulation. Periodontitis may be a critical factor in the progress of nephropathy in diabetic patients.

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Section: Animalsmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

Section: Immunohistochemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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