Role of glomerular proteoglycans in IgA nephropathy.
Role of glomerular proteoglycans in IgA nephropathy.
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DOI：
10.1371/journal.pone.0018575
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发表时间：
2011-04-06
期刊：
影响因子：
3.7
通讯作者：
Nyström J
中科院分区：
文献类型：
--
作者：
Ebefors K;Granqvist A;Ingelsten M;Mölne J;Haraldsson B;Nyström J
系膜基质扩张是最常见的肾小球肾炎IgA肾病（IgAN）的一个显著特征。为了寻找分子标记，提高对该病的认识，我们在IgAN患者的活检中研究了蛋白聚糖的基因和蛋白表达，并将其与临床和形态学数据相关联。我们收集了IgAN患者（n = 19）和健康肾脏供者（n = 14）的肾脏活检并进行了显微解剖。患者平均随访时间为4年，血压符合目标指南。在肾小球和小管间质细胞中可见不同的基因表达模式。研究发现，三种蛋白多糖在肾小球中具有特殊的意义和上调：perlecan、decorin和biglycan。Perlecan基因表达与白蛋白排泄及疾病进展呈负相关。在硬化肾小球中发现丰富的decorin蛋白表达，但在IgAN患者或对照组未受影响的肾小球中没有。与perlecan、decorin和biglycan相互作用的转化生长因子β (TGF-β)在肾小球中的基因和蛋白水平均上调。本研究为IgAN系膜基质扩张的分子机制提供了进一步的见解。我们得出结论，perlecan可能是IgAN患者的预后标志物。此外，biglycan和decorin的上调，以及TGF-β本身的上调，表明TGF-β等纤维化标志物的调节在IgAN病理中起作用。
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-β), 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-β itself, indicate that regulation of TGF-β, and other profibrotic markers plays a role in IgAN pathology.
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影响因子：
64.8
作者：
BORDER, WA;NOBLE, NA;RUOSLAHTI, E
通讯作者：
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