Further studies are required to elucidate the detailed mechanisms. In summary, we hypothesised that Cnm-positive harboured in the oral cavity induced immunoreactions that potentially led to the occurrence of IgAN-like lesions in rats. cells and mesangial matrix. These results suggest that IgAN-like glomerulonephritis was induced in rats with severe dental caries by Cnm-positive is a Gram-positive facultative anaerobic bacterium and a major causative agent of dental caries1. occasionally induces infective endocarditis after invasion of the bloodstream during invasive dental procedures such as tooth extractions2. The surface 120?kDa collagen-binding protein (Cnm) mediates adhesion to and invasion of vascular endothelial cells, which contributes to infective endocarditis3,4. The gene is detected at a high frequency in strains are associated with deterioration of patients with systemic diseases such as cerebral haemorrhage, ulcerative colitis, and non-alcoholic steatohepatitis6C11. Immunoglobulin A nephropathy (IgAN) is the most common chronic form of primary glomerulonephritis. Approximately 30%C40% of IgAN patients progress to end-stage kidney disease within 20 years12C14. The major clinical findings of IgAN are proteinuria and haematuria15C17, while common histopathological findings include proliferation of mesangial cells and mesangial matrix in the glomerulus18. Deposition of IgA and complement C3 in mesangial regions and electron dense deposits (EDDs) in the mesangial matrix are characteristic of IgAN19. However, the detailed pathogenesis of the disease is poorly understood. IgAN patients often show deterioration of macroscopic haematuria in mucosal infections19. Immune dysregulation in the upper airway mucosa due to infection by is believed to cause glomerular tissue damage20C22. Several case reports have described prior infection of the Importazole upper airway mucosa in patients with acute IgAN23. A recent review has also suggested that mucosal alterations such as infections activate the innate immune system, aggravate pre-existing IgAN, and promote disease manifestations such as macrohaematuria21. Periodontal bacteria such as spp. and have been implicated in the development of IgAN24,25 and a microbiome study has shown that changes in the subgingival microbial structure and IgAN correlate in patients with chronic periodontitis26, although the underlying mechanisms remain unclear. In some studies, nephritis has been induced in rabbits by intravenous administration of proteins27. Recently, we Importazole found Cnm-positive at a high frequency in the oral cavities of IgAN patients28. Additionally, IgAN patients that harbour Cnm-positive show significantly higher numbers of caries-experienced teeth and more severe proteinuria29. Our recent study demonstrated that intravenous administration of Cnm-positive transiently induces an IgAN-like condition in rats30. In the present study, we assessed whether IgAN-like conditions were also observed in a rat model of dental caries. Results Development of a rat model of severe dental caries We used a streptomycin-resistant Cnm-positive strain isolated from an IgAN patient (SN74R) and a streptomycin-resistant Cnm-negative strain isolated from a healthy child (MT8148R) to evaluate the intensity of dental caries in rats. Our first attempts using a conventional strategy of feeding for 11?weeks produced only mild dental caries. Thus, we fed the rats for extended periods of 16, 24, 32, and 40?weeks Importazole in an attempt to model severe dental caries. Rats fed for 16?weeks showed no lesions that extended to the pulp space, whereas 60% of rats fed for 24?weeks showed severe dental caries that extended to the pulp space. All rats fed for 32?weeks showed severe Rabbit Polyclonal to VAV3 (phospho-Tyr173) dental caries that extended to the pulp space. Rats fed for 40?weeks showed more severe dental caries lesions, although the status of dental caries could not be evaluated because the tooth crown was completely destroyed. Therefore, we used a maximum feeding period of 32?weeks. Rats were fed for 16, 24, and 32?weeks and then kidney tissues were collected, which showed that the rates of IgA nephropathy-like glomerulonephritis lesions evaluated by histopathological and immunochemical staining using an anti-IgA antibody were 4.2% (1/24), 26.1% (6/23,) and 51.7% (15/29), respectively. Thus, we used a feeding period of 32?weeks for the following experiments. Oral conditions after treatment In rats fed for 32?weeks, dental plaque accumulation was prominent in both the Cnm-positive group (SN74R) and Cnm-negative group (MT8148R) compared Importazole with the control group (Fig.?1a). The dental plaque scores of rats.
