title: Urinary exosome-derived microRNAs reflecting the changes of renal function and histopathology in dogs.
abstract: MicroRNAs act as post-transcriptional regulators, and urinary exosome (UExo)-derived microRNAs may be used as biomarkers. Herein, we screened for UExo-derived microRNAs reflecting kidney disease (KD) status in dogs. Examined dogs were divided into healthy kidney control (HC) and KD groups according to renal dysfunction. We confirmed the appearance of UExo having irregular globe-shapes in a dog by immunoblot detection of the exosome markers, TSG101 and CD9. Based on our previous data using KD model mice and the data obtained herein by next generation sequencing of UExo-derived microRNAs in dogs, miR-26a, miR-146a, miR-486, miR-21a, and miR-10a/b were selected as candidate microRNAs. In particular, UExo-derived miR-26a and miR-10a/b were significantly decreased in KD dogs, and miR-26a levels negatively correlated with deteriorated renal function compared to the other miRNAs. UExo-derived miR-21a levels corrected or not to that of internal control microRNAs in UExo, miR-26a and miR-191, significantly increased with renal dysfunction. In kidney tissues, the decrease of miR-26a and miR-10a/b in the glomerulus and miR-10b in the tubulointerstitium negatively correlated with deteriorated renal function and histopathology. Increased miR-21a in the tubulointerstitium rather than in the glomerulus correlated with deteriorated renal histopathology. In conclusion, microRNAs reflecting the changes in renal function and histopathology in dogs were identified in this study.
authors.affiliation: Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ichii
authors.affiliation: Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohta
authors.affiliation: Department of Endocrinology, Metabolism and Nephrology, Kochi University School of Medicine, Kohasu, Oko-cho, Nankoku 783-8505, 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, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan.|Section of Biological Safety Research, Chitose Laboratory, Japan Food Research Laboratories, Bunkyo 2-3, Chitose 066-0052, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan.
authors.forename: Marina
authors.initials: M
authors.lastname: Hosotani
authors.affiliation: Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Mizoguchi
authors.affiliation: Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Morishita
authors.affiliation: Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hoshino
authors.affiliation: Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takagi
authors.affiliation: Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Sasaki
authors.affiliation: Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Takiguchi
authors.affiliation: Matsubara Animal Hospital, Taijo 1-174-1, Matsubara 580-0044, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Sato
authors.affiliation: Matsubara Animal Hospital, Taijo 1-174-1, Matsubara 580-0044, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Oyamada
authors.affiliation: Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kon
mesh_terms: D000818:Animals; D004285:Dogs; D055354:Exosomes / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology*; D007674:Kidney Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D035683:MicroRNAs / Q000652:urine*
chemical_list: D035683:MicroRNAs