{Reference Type}: Journal Article {Title}: Fusobacterium nucleatum-infected periodontitis promotes renal interstitial fibrosis in rats through the TGF-β/SMAD2/3 and β-catenin signaling pathways. {Author}: Chen P;Lin X;Zhang C;Xie Y;Guo Z;Ren F; {Journal}: Gene {Volume}: 927 {Issue}: 0 {Year}: 2024 Nov 15 {Factor}: 3.913 {DOI}: 10.1016/j.gene.2024.148729 {Abstract}: OBJECTIVE: Periodontitis is associated with Fusobacterium nucleatum (F.n) infection. Although the colonization of renal tissue by F.n is well documented, its specific role in kidney disease has yet to be determined. This study aimed to investigate the potential association between F.n-induced periodontitis and renal interstitial fibrosis.
METHODS: The rat gingival sulcus was injected with F.n suspension, while the control group (NC) was injected with PBS. The levels of total protein (TP), albumin (ALB), creatinine, and urea nitrogen (BUN) in rat serum and/or urine were quantified using the appropriate kits. Renal interstitial fibrosis and epithelial-mesenchymal transition (EMT) were evaluated in rats using Masson staining, Periodic Schiff-Methenamine (PASM) staining, and immunohistochemical staining. The levels of fibrosis- and EMT-related proteins and the TGF-β/SMAD2/3 and β-catenin signaling pathways were determined using Western blot analysis. F.n in the kidney tissues was quantitatively determined using bacterial 16S rRNA technology.
RESULTS: Serum levels of TP, ALB, creatinine, and BUN were not significantly decreased in F.n-infected rats with periodontitis. The levels of creatinine and ALB in the urine were not statistically different between two groups. Masson and PASM staining showed that F.n-induced periodontitis could promote renal interstitial fibrosis in rats. The levels of collagen I, fibronectin (FN), vimentin, and α-SMA were upregulated in the kidney tissues of rats with F.n-induced periodontitis and in F.n-treated HK-2 cells. However, E-cadherin levels were reduced. F.n promoted renal interstitial and HK-2 cell fibrosis in rats by modulating the TGF-β/SMAD2/3 and β-catenin signaling pathways. F.n colonization increased renal interstitial fibrosis in rats.
CONCLUSIONS: F.n-induced periodontitis promoted EMT by activating the TGF-β/SMAD2/3 and β-catenin signaling pathways, thus promoting renal interstitial fibrosis in rats.