title: Overexpression of Toll-like receptor 8 correlates with the progression of podocyte injury in murine autoimmune glomerulonephritis.
abstract: Members of the Toll-like receptor (TLR) family serve as pathogen sensors and participate in local autoimmune responses. This study found a correlation between glomerular injury and TLR expression by analysing BXSB/MpJ-Yaa (BXSB-Yaa) lupus model mice. In isolated glomeruli, the mRNA expression of several TLRs was higher in BXSB-Yaa mice than in healthy control BXSB mice. In particular, the expression of Tlr8 and its downstream cytokines was markedly increased. In mouse kidneys, TLR8 protein and mRNA localized to podocytes, and TLR8 protein expression in the glomerulus was higher in BXSB-Yaa mice than in BXSB mice. In BXSB-Yaa mice, the glomerular levels of Tlr8 mRNA negatively correlated with the glomerular levels of podocyte functional markers (Nphs1, Nphs2, and Synpo) and positively correlated with urinary albumin levels. Furthermore, the glomerular and serum levels of miR-21, a putative microRNA ligand of TLR8, were higher in BXSB-Yaa mice than in BXSB mice. The urinary levels of Tlr8 mRNA were also higher in BXSB-Yaa mice than in BXSB mice. In conclusion, the overexpression of TLR8 correlates with the progression of podocyte injury in glomerulonephritis. Thus, altered levels of urinary Tlr8 mRNA might reflect podocyte injury.
authors.affiliation: Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Junpei
authors.initials: J
authors.lastname: Kimura
authors.affiliation: Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ichii
authors.affiliation: Laboratory of Molecular Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Miyazono
authors.affiliation: 1] Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan [2] Section of Biological Safety Research, Chitose Laboratory, Japan Food Research Laboratories, Chitose, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Horino
authors.affiliation: Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Otsuka-Kanazawa
authors.affiliation: Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kon
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005921:Glomerulonephritis / Q000235:genetics* / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D050199:Podocytes / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D051200:Toll-Like Receptor 8 / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; C552579:TLR8 protein, mouse; D051200:Toll-Like Receptor 8