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Changes in glomerular mesangium in kidneys with congenital nephrotic syndrome of the Finnish type

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Abstract

Congenital nephrotic syndrome of the Finnish type (NPHS1, CNF) is an autosomal recessive disease caused by mutations in a major podocyte protein, nephrin. NPHS1 is associated with heavy proteinuria and the development of glomerular scarring. We studied the cellular and molecular changes affecting the glomerular mesangium in NPHS1 kidneys. Marked hyperplasia of mesangial cells (MC) was mainly responsible for the early mesangial expansion in NPHS1 glomeruli. The levels of the proliferation marker, mindbomb homolog 1 and the major MC mitogen, platelet-derived growth factor, and its receptors, however, were quite normal. Only a small number of cells were positive for CD68 (marker for phagocytic cells) and CD34 (marker for mesenchymal precursor cells) in the NPHS1 mesangium. MCs strongly expressed α-smooth muscle actin, indicating myofibloblast transformation. The expression levels of the profibrotic mediators osteopontin and transforming growth factor β were up-regulated in NPHS1 glomeruli by 3.2 and 1.6-fold, respectively, compared to the controls. The synthesis by MCs of the typical fibroblast products collagen I, fibronectin, and tenascin, however, was low, and the extracellular matrix increase was caused by the accumulation of a normal MC product, collagen IV. The results indicate that severe glomerular sclerosis can develop without major qualitative cellular or molecular changes in the mesangium.

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Acknowledgments

We warmly thank Tuike Helmiö for her excellent technical assistance.

Confilct of Interest

The authors declare that they have no competing interest.

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Authors and Affiliations

  1. Children’s Hospital and Biomedicum Helsinki, University of Helsinki, P.O.Box 20, 00014, Helsinki, Finland

    Anne Kaukinen, Arvi-Matti Kuusniemi & Hannu Jalanko

  2. Department of Pathology, University of Helsinki, Helsinki, Finland

    Heikki Helin

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  1. Anne Kaukinen
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  2. Arvi-Matti Kuusniemi
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  3. Heikki Helin
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  4. Hannu Jalanko
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Correspondence to Anne Kaukinen.

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Kaukinen, A., Kuusniemi, AM., Helin, H. et al. Changes in glomerular mesangium in kidneys with congenital nephrotic syndrome of the Finnish type. Pediatr Nephrol 25, 867–875 (2010). https://doi.org/10.1007/s00467-009-1385-5

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  • DOI: https://doi.org/10.1007/s00467-009-1385-5

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