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Transmembrane collagen XVII is a novel component of the glomerular filtration barrier

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Abstract

The kidney filtration barrier consists of the capillary endothelium, the glomerular basement membrane and the slit diaphragm localized between foot processes of neighbouring podocytes. We report that collagen XVII, a transmembrane molecule known to be required for epithelial adhesion, is expressed in podocytes of normal human and mouse kidneys and in endothelial cells of the glomerular filtration barrier. Immunoelectron microscopy has revealed that collagen XVII is localized in foot processes of podocytes and in the glomerular basement membrane. Its role in kidney has been analysed in knockout mice, which survive to birth but have high neonatal mortality and skin blistering and structural abnormalities in their glomeruli. Morphometric analysis has shown increases in glomerular volume fraction and surface densities of knockout kidneys, indicating an increased glomerular amount in the cortex. Collagen XVII deficiency causes effacement of podocyte foot processes; however, major slit diaphragm disruptions have not been detected. The glomerular basement membrane is split in areas in which glomerular and endothelial basement membranes meet. Differences in the expression of collagen IV, integrins α3 or β1, laminin α5 and nephrin have not been observed in mutant mice compared with controls. We propose that collagen XVII has a function in the attachment of podocyte foot processes to the glomerular basement membrane. It probably contributes to podocyte maturation and might have a role in glomerular filtration.

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Acknowledgements

We thank Ms Anja Mattila, Ms Seija Leskelä, Ms Annikki Huhtela and the personnel of the Biocenter Oulu EM and transgenic core facility for expert technical assistance. Dr. Pentti Nieminen and Risto Bloigu are acknowledged for their excellent advice on statistics, and Dr. Sinikka Eskelinen is acknowledged for her expertise in confocal microscopy.

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Authors and Affiliations

  1. Department of Dermatology, Oulu Center for Cell-Matrix Research, University of Oulu, Aapistie 5A, FIN-90220, Oulu, Finland

    Tiina Hurskainen, Jyri Moilanen, Laura Huilaja & Kaisa Tasanen

  2. Clinical Research Center, Oulu University Hospital, Aapistie 5A, FIN-90220, Oulu, Finland

    Tiina Hurskainen, Jyri Moilanen, Laura Huilaja & Kaisa Tasanen

  3. Biocenter Oulu, University of Oulu, Aapistie 5A, FIN-90220, Oulu, Finland

    Raija Sormunen & Raija Soininen

  4. Department of Pathology, University of Oulu, Aapistie 3, FIN-90220, Oulu, Finland

    Raija Sormunen

  5. Department of Dermatology, University Medical Center Freiburg and Freiburg Institute of Advanced Studies, School of Life Sciences, 79104, Freiburg, Germany

    Claus-Werner Franzke, Stefanie Loeffek & Leena Bruckner-Tuderman

  6. Department of Pathology, University of Oulu, Oulu University Hospital, Aapistie 3, FIN-90220, Oulu, Finland

    Helena Autio-Harmainen

  7. Department of Medical Biochemistry and Molecular Biology, Oulu Center for Cell-Matrix Research, University of Oulu, Aapistie 3, FIN-90220, Oulu, Finland

    Raija Soininen

  8. Department of Paediatrics, Oulu University Hospital, Kajaanintie 52, FIN-90220, Oulu, Finland

    Matti Nuutinen

Authors
  1. Tiina Hurskainen
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  2. Jyri Moilanen
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  3. Raija Sormunen
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  4. Claus-Werner Franzke
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  5. Raija Soininen
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  6. Stefanie Loeffek
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  7. Laura Huilaja
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  8. Matti Nuutinen
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  9. Leena Bruckner-Tuderman
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  10. Helena Autio-Harmainen
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  11. Kaisa Tasanen
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Corresponding author

Correspondence to Tiina Hurskainen.

Additional information

This study was supported by the Finnish Medical Society Duodecim of Oulu, Northern Finland Cancer Foundation, Finnish Cultural Foundation, Oulu University Hospital and Academy of Finland grants to K.T., Oulu University Hospital grant to H.A-H. and a German Research Foundation (DFG) grant (SFB-850/B6) to L. B-T. and C.-W.F.

T. Hurskainen and J. Moilanen contributed equally to this work.

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Figure S 1

Demonstration of an intact slit diaphragm (SD) of Col17a1 -/- podocytes (P). Transmission electron microscopy demonstrates an intact SD (arrow) between two podocyte cells in Col17a1 -/- mice (BM basement membrane, E endothelial cell). (JPEG 173 kb)

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Hurskainen, T., Moilanen, J., Sormunen, R. et al. Transmembrane collagen XVII is a novel component of the glomerular filtration barrier. Cell Tissue Res 348, 579–588 (2012). https://doi.org/10.1007/s00441-012-1368-x

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  • DOI: https://doi.org/10.1007/s00441-012-1368-x

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