MRL/MpJ mice show unique pathological features after experimental kidney injury.
Clarification of the renal repair process is crucial for developing novel therapeutic strategies for kidney injury. MRL/MpJ mice have a unique repair process characterized by low scar formation. The pathological features of experimentally injured MRL/MpJ and C57BL/6 mouse kidneys were compared to examine the renal repair process. The dilation and atrophy of renal tubules were observed in folic acid (FA)-induced acute kidney injury (AKI) in both strains, and the histopathological injury scores and number of interleukin (IL)-1F6-positive damaged distal tubules and kidney injury molecule 1 (KIM-1)-positive damaged proximal tubules drastically increased 1 day after AKI induction. However, KIM-1-positive tubules and the elevation of serum renal function markers were significantly fewer and lower, respectively, in MRL/MpJ mice at days 2 and 7 after AKI. After traumatic kidney injury (TKI) via needle puncture, severe tubular necrotic lesions in the punctured area and fibrosis progressed in both strains. Indices for fibrosis such as aniline blue-positive area, number of alpha smooth muscle actin-positive myofibroblasts, and messenger RNA expression levels of Tgfb1 and Mmp2 indicated lower fibrotic activity in MRL/MpJ kidneys. Characteristically, only MRL/MpJ kidneys manifested remarkable calcification around the punctured area beginning 7 days after TKI. The pathological features of injured MRL/MpJ and C57BL/6 kidneys differed, especially those of kidneys with mild proximal tubular injuries after FA-induced AKI. Lower fibrotic activity and increased calcification after TKI were observed in MRL/MpJ kidneys. These findings clarified the unique pathological characteristics of MRL/MpJ mouse kidneys and contribute to understanding of the renal repair process after kidney injury.
Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Hokkaido, Japan.
Daichi
D
Shiozuru
Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Hokkaido, Japan.
Osamu
O
Ichii
Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Hokkaido, Japan.
Junpei
J
Kimura
Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University and Section of Biological Safety Research, Chitose Laboratory, Japan Food Research Laboratories, Chitose, Hokkaido, Japan.
Teppei
T
Nakamura
Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Hokkaido, Japan and Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
Yaser Hosny Ali
YH
Elewa
Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Hokkaido, Japan.
Saori
S
Otsuka-Kanazawa
Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Hokkaido, Japan. y-kon@vetmed.hokudai.ac.jp.
Yasuhiro
Y
Kon
D058186:Acute Kidney Injury / Q000503:physiopathology*; D000818:Animals; D002114:Calcinosis / Q000473:pathology; D004195:Disease Models, Animal; D005355:Fibrosis; D005492:Folic Acid / Q000009:adverse effects; D007668:Kidney / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D007674:Kidney Diseases / Q000503:physiopathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010641:Phenotype; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014945:Wound Healing
C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D005492:Folic Acid; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse