Role of podocyte slit diaphragm as a filtration barrier (Review Article)

Authors

  • HIROSHI KAWACHI,

    Corresponding author
    1. Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, and
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  • NAOKO MIYAUCHI,

    1. Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, and
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  • KOICHI SUZUKI,

    1. Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, and
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  • GI DONG HAN,

    1. Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, and
    2. Department of Food Science and Technology, Yeungnam University, Gyeongsan, Republic of Korea
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  • MICHIAKI ORIKASA,

    1. Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, and
    2. Department of Biomedical Technology, School of Health Science, Faculty of Medicine, Niigata University, Niigata, Japan; and
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  • FUJIO SHIMIZU

    1. Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, and
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Dr Hiroshi Kawachi, Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Science, 1-757 Asahimachi-dori, Niigata 951-8510, Japan. Email: kawachi@med.niigata-u.ac.jp

Abstract

SUMMARY:  Although the role of glomerular basement membrane has been emphasised as the barrier for retaining plasma proteins in the past three decades, some recent studies have demonstrated that the slit diaphragm of the glomerular epithelial cell (podocyte) is the structure likely to be the barrier in the glomerular capillary wall. Nephrin and podocin were identified as gene products mutated in Finnish-type congenital nephrotic syndrome and autosomal recessive steroid-resistant nephrotic syndrome, respectively. Nephrin s located at the outer leaflet of plasma membranes of the slit diaphragm. Podocin is reported to have an interaction with nephrin. The anti-nephrin antibody is capable of inducing massive proteinuria, which indicates that nephrin is a key functional molecule in the slit diaphragm. The expression of nephrin and podocin was reduced in glomeruli of minimal change nephrotic syndrome, which suggested that the altered expression of these molecules contributes to the development of proteinuria also in acquired diseases. Some recent studies demonstrated that CD2-associated protein (CD2AP) is also a functional molecule in the slit diaphragm, and its expression is altered in membranous nephropathy. These observations suggested that alteration of the molecular arrangement in the slit diaphragm is involved in the development of proteinuria in several kinds of glomerular diseases.

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