From Cell Biology to Tissue Engineering


MRL/MpJ mice show unique pathological features after experimental kidney injury

Daichi Shiozuru1, Osamu Ichii1, Junpei Kimura1, Teppei Nakamura1,2, Yaser Hosny Ali Elewa1,3, Saori Otsuka-Kanazawa1 and Yasuhiro Kon1

1Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, 2Section of Biological Safety Research, Chitose Laboratory, Japan Food Research Laboratories, Chitose, Hokkaido, Japan and 3Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt

Offprint requests to: Yasuhiro Kon, Laboratory of Anatomy, Department of Biomedical Sciences, School of Veterinary Medicine, Hokkaido University, Kita 18-Nishi 9 Kita-ku, Sapporo, 060-0818, Japan. e-mail: y-kon@vetmed.hokudai.ac.jp

Summary. 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. Histol Histopathol 31, 189-204 (2016)

Key words: Fibrosis, Kidney, MRL/MpJ mice, Repair

DOI: 10.14670/HH-11-662