Mesangial proliferation scores were calculated on the basis of the percentage of 50 glomeruli with mesangial cell and matrix proliferation in PAS-stained sections30. Kidney diseases, Nephritis, Pathogenesis, Infection, Medical research, Experimental models of disease, Diseases, Dental diseases, Kidney diseases, Oral diseases == Introduction == Streptococcus mutansis a Gram-positive facultative anaerobic bacterium and a major causative agent of dental caries1.S. mutansoccasionally induces infective endocarditis after invasion of the bloodstream during invasive dental procedures such as tooth extractions2. TheS. mutanssurface 120 kDa collagen-binding protein (Cnm) mediates adhesion to and invasion of vascular endothelial cells, which contributes to infective endocarditis3,4. Thecnmgene is detected at a high frequency inS. mutans-positive heart valve specimens from patients with infective endocarditis5. Additionally,cnm-positiveS. mutansstrains are associated with deterioration of patients with systemic diseases such as cerebral haemorrhage, ulcerative colitis, and non-alcoholic FGF18 steatohepatitis611. Immunoglobulin A nephropathy (IgAN) is the most common chronic form of primary glomerulonephritis. Approximately 30%40% of IgAN patients progress to end-stage kidney disease within 20 years1214. The major clinical findings of IgAN are proteinuria and haematuria1517, while common histopathological findings include proliferation of mesangial cells and mesangial matrix in the glomerulus18. Deposition of IgA and complement Fluvastatin 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 byEscherichia coli,Pseudomonas aeruginosa, Haemophilus parainfluenzae, and methicillin-resistantStaphylococcus aureusis believed to cause glomerular tissue damage2022. Several case reports have described prior infection of the 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 asTreponemaspp. andCampylobacter rectushave Fluvastatin been implicated in the development of IgAN24,25and 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 Fluvastatin rabbits by intravenous administration ofS. mutansproteins27. Recently, we found Cnm-positiveS. mutansat a high frequency in the oral cavities of IgAN patients28. Additionally, IgAN patients that harbour Cnm-positiveS. mutansshow significantly higher numbers of caries-experienced teeth and more severe proteinuria29. Our recent study demonstrated that intravenous administration of Cnm-positiveS. mutanstransiently 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 Fluvastatin 16, 24, 32, and 40 weeks 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 dental care caries that prolonged to the pulp space. Rats fed for 40 weeks showed more severe dental care caries lesions, even though status of dental care 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 cells were collected, which showed 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. Therefore, we used a feeding period of 32 weeks for the Fluvastatin following experiments. == Oral conditions after treatment == In rats fed for 32 weeks, dental care plaque build up was prominent in both the Cnm-positive group (SN74R) and Cnm-negative group (MT8148R) compared with the control group (Fig.1a). The dental care plaque scores of rats inoculated with Cnm-negativeS. mutanswere the highest, followed by rats inoculated with Cnm-positiveS. mutans. The scores of both organizations were significantly greater than those of the control group (P< 0.001) (Fig.1b). Only attrition and minor dental care caries were observed in the control group, whereas severe dental care caries were observed in Cnm-positive and Cnm-negative organizations (Fig.1c). The dental care caries scores of.