Kidney Week

Abstract: FR-PO953

Mitochondrial Morphological Abnormality in Cyst Epithelial Cells of Autosomal Dominant Polycystic Kidney Disease Patients

Session Information

• PKD Cellular Pathogenesis, ARPKD, ADTKD, Ciliopathies
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidney

• 1001 Genetic Diseases of the Kidney: Cystic

Authors

• Ishimoto, Yu, University of Tokyo School of Medicine, Tokyo, Japan

Yu Ishimoto,

• Nangaku, Masaomi, University of Tokyo School of Medicine, Tokyo, Japan

Masaomi Nangaku,

• Nishio, Saori, Hokkaido University, Sapporo, Japan

Saori Nishio,

• Kawano, Haruna, Juntendo university, Tokyo, Japan

Haruna Kawano,

• Horie, Shigeo, Juntendo University, Tokyo, Japan

Shigeo Horie,

• Kasahara, Tomoko, Kyoto University, Kyoto, Japan

Tomoko Kasahara,

• Osafune, Kenji, Center for iPS Cell Research and Application, Kyoto University, Kyoto City, Kyoto, Japan

Kenji Osafune,

• Hoshino, Junichi, Toranomon Hospital, Tokyo, Japan

Junichi Hoshino,

• Ubara, Yoshifumi, Toranomon Hospital, Tokyo, Japan

Yoshifumi Ubara,

• Shimizu, Akira, Nippion Medical School, Tokyo, Japan

Akira Shimizu,

• Kugita, Masanori, Fujita Health University, Toyoake, Aichi-KEN, Japan

Masanori Kugita,

• Nagao, Shizuko, Fujita Health University, Toyoake, Aichi-KEN, Japan

Shizuko Nagao,

• Honda, Kenjiro, University of Tokyo School of Medicine, Tokyo, Japan

Kenjiro Honda,

• Inagi, Reiko, University of Tokyo School of Medicine, Tokyo, Japan

Reiko Inagi,

Background

Recent studies reported that polycystin-1 affects mitochondrial function directly or indirectly and facilitates pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). However, it is not confirmed in the kidney of ADPKD patients.

Methods

We conducted multi-center study, collected the kidney tissues from 20 ADPKD patients (this study was approved by the research ethics committees of the Graduate School of Medicine and Faculty of Medicine, The University of Tokyo. No.11560-(2)). By transmission electron microscopy, mitochondrial morphology was assessed in the kidney from ADPKD patients or ADPKD model animals. Quantification of mitochondrial morphology was done using ImageJ software.

Results

In cyst epithelial cells with cuboidal shape, mitochondria are abundant. In contrast, in the cyst epithelial cells, which reduce their height, the number of mitochondria was decreased, and subsequently, mitochondria are almost gone in the cyst epithelial cells with flat shape. The mean volume of the cyst epithelial cells of ADPKD patients (mtADPKD) were about 1.2 times larger than in the tubules of normal human control (mtCON). Mitochondria of mtCON exhibited a wide variety of morphologies (elongated and fragmented), however that of mtADPKD showed almost uniform with round shape. In addition, mtADPKD showed indistinct cristae formation. These characteristics of abnormal mitochondrial shape are the same with that observed in the cyst epithelial cells of Pkd1^flox/flox:Ksp-Cre mice and Pax8^rtTA;TetO-Cre;Pkd2^lox/flox mice but different from that of Cy/+ rat.

Conclusion

Our results indicate that mitochondria in the cyst epithelial cells of ADPKD patients swollen with indistinct cristae formation and this might be the characteristics of polycystin-1 or polycystin-2 dysfunction in the kidney of ADPKD patients. Mitochondrial dynamics serves a variety of different functions, including cell proliferation. Similar mitochondrial morphological change was observed in cancer cells and which might reflect pathological derangements characteristic of ADPKD has marked similarities to those of solid tumors.

Funding

• Government Support - Non-U.S.