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Podocyte penetration of the glomerular basement membrane to contact on the mesangial cell at the lesion of mesangial interposition in lupus nephritis: a three-dimensional analysis by serial block-face scanning electron microscopy

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Abstract

Background

The interaction among the glomerular components plays an important role in the development of glomerular lesions; thus, investigation of the ultrastructural three-dimensional (3D) configuration of the human glomerular cells and extracellular matrix (ECM) is important for understanding the pathogenesis of glomerulosclerosis, especially glomerulonephritis.

Methods

We applied a new technique of serial block-face scanning electron microscopy (SBF-SEM), which helps to acquire serial electron microscopic images to reconstruct a 3D ultrastructure, to a human kidney biopsy specimen obtained from a 25-year-old woman with lupus nephritis.

Results

SBF-SEM demonstrated that the cytoplasmic processes of the podocyte penetrated into the lamina densa of the glomerular basement membrane, and was in direct contact with the cytoplasm of mesangial cells at the site of mesangial interposition.

Conclusion

Although this is a single-case observational study, SBF-SEM revealed a unique 3D configuration, suggesting a novel mechanism of direct intercellular cross-communication between podocytes and mesangial cells, aside from the presumed paracrine communication.

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Acknowledgements

We thank Professor Kazuho Honda of the Department of Anatomy, Showa University School of Medicine for the critical reading and helpful suggestions; Drs. Truc Quynh Thai and Huy Bang Nguyen of the Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki, Japan for providing technical assistance; and Ms. Atsuko Imai of the Division of Cell Structure, National Institute for Physiological Sciences, Okazaki, Japan for her kind support in the segmentation and 3D techniques. The authors would like to thank Enago (http://www.enago.jp) for the English language review.

Funding

This work was partly supported by the JSPS KAKENHI Grant (number 26460449) to KJ; the Cooperative Research Program of Network Joint Research Center for Materials and Devices granted to KJ, MN, and TT; and a Grant-in-Aid for Scientific Research on Innovative Areas-Resource and technical support platforms for promoting research of Advanced Bioimaging Support (JP16H06280) to KJ, MN, and TT.

Author information

Authors and Affiliations

  1. Division of Electron microscopy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan

    Takashi Takaki

  2. Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi Aoba-ku, Sendai-shi, Miyagi-ken, 980-8575, Japan

    Takashi Takaki & Kensuke Joh

  3. Division of Histology and Cell Biology, School of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi-ken, 329-0431, Japan

    Nobuhiko Ohno

  4. Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, 5-1 Higashiyama, Myoudaiji-cho, Okazaki-shi, Aichi-ken, 444-8787, Japan

    Nobuhiko Ohno

  5. Section of Electron Microscopy, Supportive Center for Brain Research, National Institute for Physiological Sciences, Okazaki-shi, Aichi-ken, 444-8787, Japan

    Sei Saitoh

  6. Department of Anatomy II and Cell Biology, Fujita Health University School of Medicine, 1-98 Dengakubo, Kutsukake-cho, Toyoake-shi, Aichi-ken, 470-1192, Japan

    Sei Saitoh

  7. Division of Nephrology, Narita Memorial Hospital, 134 Haneihonmachi, Toyohashi-shi, Aichi-ken, 441-8029, Japan

    Masaaki Nagai

Authors
  1. Takashi Takaki
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  2. Nobuhiko Ohno
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  3. Sei Saitoh
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  4. Masaaki Nagai
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  5. Kensuke Joh
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Contributions

MN was the attending physician of the patient. KJ, NO, and TT wrote the manuscript. NO, SS, and TT performed the genetic analyses. TT performed the observation with the TEM. NO, SS, and TT performed the observation with the SBF-SEM. KJ is a renal pathologist who helped diagnose the patient. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Takashi Takaki.

Ethics declarations

Ethical approval

All procedures that involved human participants were performed in accordance with the ethical standards of the institution at which the study was conducted (IRB approval number 2015-1-514, Tohoku University School of Medicine) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Conflict of interest

The authors have declared that no conflict of interest exists.

Informed consent

Informed consent was obtained from all participants in the study.

Consent for publication

The patient gave informed consent for data publication.

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Takaki, T., Ohno, N., Saitoh, S. et al. Podocyte penetration of the glomerular basement membrane to contact on the mesangial cell at the lesion of mesangial interposition in lupus nephritis: a three-dimensional analysis by serial block-face scanning electron microscopy. Clin Exp Nephrol 23, 773–781 (2019). https://doi.org/10.1007/s10157-019-01701-0

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  • DOI: https://doi.org/10.1007/s10157-019-01701-0

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