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Role of glomerular proteoglycans in IgA nephropathy

Journal article
Authors Kerstin Ebefors
Anna Björnson Granqvist
Madeleine Ingelsten
Johan Mölne
Börje Haraldsson
Jenny Nyström
Published in PLoS ONE
Volume 6
Issue 4
Pages e18575
ISSN 1932-6203
Publication year 2011
Published at Institute of Biomedicine, Department of Pathology
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages e18575
Language en
Links dx.doi.org/10.1371/journal.pone.001...
Subject categories Physiology, Kidney diseases

Abstract

Mesangial matrix expansion is a prominent feature of the most common form of glomerulonephritis, IgA nephropathy (IgAN). To find molecular markers and improve the understanding of the disease, the gene and protein expression of proteoglycans were investigated in biopsies from IgAN patients and correlated to clinical and morphological data. We collected and microdissected renal biopsies from IgAN patients (n = 19) and from healthy kidney donors (n = 14). Patients were followed for an average time of 4 years and blood pressure was according to target guidelines. Distinct patterns of gene expression were seen in glomerular and tubulo-interstitial cells. Three of the proteoglycans investigated were found to be of special interest and upregulated in glomeruli: perlecan, decorin and biglycan. Perlecan gene expression negatively correlated to albumin excretion and progress of the disease. Abundant decorin protein expression was found in sclerotic glomeruli, but not in unaffected glomeruli from IgAN patients or in controls. Transforming growth factor beta (TGF-beta), known to interact with perlecan, decorin and biglycan, were upregulated both on gene and protein level in the glomeruli. This study provides further insight into the molecular mechanisms involved in mesangial matrix expansion in IgAN. We conclude that perlecan is a possible prognostic marker for patients with IgAN. In addition, the up-regulation of biglycan and decorin, as well as TGF-beta itself, indicate that regulation of TGF-beta, and other profibrotic markers plays a role in IgAN pathology.

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