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Hemopexin in Minimal Change Nephrotic Syndrome

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Molecular Mechanisms in the Pathogenesis of Idiopathic Nephrotic Syndrome

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Abstract

Hemopexin (Hpx) is an abundant plasma protein binding to heme with the highest known affinity. A vasoactive plasma factor 100KF was originally found to be closely related to the pathogenesis of minimal change nephrotic syndrome (MCNS). 100KF was later found to be Hpx. The active isoform of Hpx is increased in children with MCNS. It has been shown to have serine protease activity and have dramatic effects on the glomerular filtration barrier. Hpx reduces sialoglycoproteins in glomerular extracellular matrix and glycocalyx on the surface of glomerular endothelial cells associated with an increase in the flux of albumin. In vivo, Hpx induced reversible proteinuria in rats, and the glomeruli had podocyte foot process effacement and reduced anionic sites along the lamina rara interna in the basement membrane similar to human MCNS. In vitro, podocytes showed dramatic reorganization of actin with loss of stress fibers after Hpx treatment. This did not occur in nephrin-deficient podocytes or in cells that do not express nephrin, specifically human glomerular endothelial cells, fibroblasts, and HEK293 cells, indicating that the Hpx effect on actin is dependent on the expression of nephrin and followed by RhoA activation and protein kinase B phosphorylation at S473 in the downstream intracellular signaling pathway. The effects were reversible and were inhibited by preincubation with human plasma and serine protease inhibitors. The possibility of proteases is discussed as circulating factors causing MCNS. The circulating inhibitory factors for active Hpx in normal physiology or the mechanisms of Hpx activation in the disease are unclear.

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Authors and Affiliations

  1. Paediatric Renal Medicine, University of Bristol, Bristol, UK

    Yasuko Kobayashi M.D., Ph.D. & Moin A. Saleem F.R.C.P., Ph.D.

  2. Department of Pediatrics, Gunma University Graduate School of Medicine, Maebashi Gunma, Japan

    Yasuko Kobayashi M.D., Ph.D.

  3. Children’s Renal Unit, Bristol Royal Hospital for Children, Paul O’Gorman Building, Upper Maudlin Street, Bristol, BS2 8BJ, UK

    Moin A. Saleem F.R.C.P., Ph.D.

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  1. Yasuko Kobayashi M.D., Ph.D.
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  2. Moin A. Saleem F.R.C.P., Ph.D.
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Correspondence to Moin A. Saleem F.R.C.P., Ph.D. .

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Editors and Affiliations

  1. Department of Pediatrics, Kansai Medical University, Hirakata, Osaka, Osaka, Japan

    Kazunari Kaneko

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Kobayashi, Y., Saleem, M.A. (2016). Hemopexin in Minimal Change Nephrotic Syndrome. In: Kaneko, K. (eds) Molecular Mechanisms in the Pathogenesis of Idiopathic Nephrotic Syndrome. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55270-3_2

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  • DOI: https://doi.org/10.1007/978-4-431-55270-3_2

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-55269-7

  • Online ISBN: 978-4-431-55270-3

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