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
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.
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.
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.
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.
KeywordsPodocyte Mesangial cell Glomerular basement membrane Serial block-face scanning electron microscopy Renal biopsy Lupus nephritis
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.
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.
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.
Compliance with ethical standards
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 was obtained from all participants in the study.
Consent for publication
The patient gave informed consent for data publication.
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