Mesangial cells from patients with IgA nephropathy have increased susceptibility to galactose-deficient IgA1

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Background:
IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, affecting close to a million people. Circulating galactose-deficient IgA (gd-IgA), present in patients with IgAN, form immune complex deposits in the glomerular mesangium causing local proliferation and matrix expansion. Intriguing though, individuals having gd-IgA deposits in the kidneys do not necessarily have signs of glomerular disease. Recurrence of IgAN only occurs in less than half of transplanted patients with IgAN, indicating that gd-IgA is not the only factor driving the disease. We hypothesize that, in addition to IgA complexes, patients with IgAN possess a subtype of mesangial cells highly susceptible to gd-IgA induced cell proliferation.

Methods:
To test the hypothesis, we designed a technique to culture primary mesangial cells from renal biopsies obtained from IgAN patients and controls. The cell response to gd-IgA treatment was then measured both on gene and protein level and the proliferation rate of the cells in response to PDGF was investigated.

Results:
When treated with gd-IgA, mesangial cells from patients with IgAN express and release more PDGF compared to controls. In addition, the mesangial cells from patients with IgAN were more responsive to treatment with PDGF resulting in an increased proliferation rate of the cells compared to control. Mesangial cells cultured from patients with IgAN expressed and released more IL-6 than controls and had a higher expression of matrix genes. Both mesangial cells derived from patients with IgAN and controls increased their expressed TGFβ1 and CCL5 when treated with gd-IgA.

Conclusion:
We conclude that mesangial cells derived from IgAN patients have a mesangioproliferative phenotype with increased reactivity to IgA and that these cellular intrinsic properties may be important for the development of IgA nephropathy.

Keywords:
Mesangial cells IgA nephropathy PDGF

Autoři: Kerstin Ebefors ^1*; Peidi Liu ¹; Emelie Lassén ²; Johannes Elvin ²; Emma Candemark ¹; Kristina Levan ³; Börje Haraldsson ²; Jenny Nyström ¹
Působiště autorů: Department of Physiology, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. ¹; Department of Molecular and Clinical Medicine, Institute of Medicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. ²; Department of Obstetrics and Gynecology, Institute of Clinical Sciences, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. ³
Vyšlo v časopise: BMC Nefrol 2016, 17:40
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1186/s12882-016-0251-5

© Ebefors et al. 2016
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
The electronic version of this article is the complete one and can be found online at: http://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-016-0251-5

Souhrn

Keywords:
Mesangial cells IgA nephropathy PDGF

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