Glomerular expression of biglycan and decorin and urinary levels of decorin in primary glomerular disease.

Glomerular expression of biglycan and decorin and urinary levels of decorin in primary glomerular disease.
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DOI:
10.5414/cnp61007
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发表时间:
2004
影响因子:
1.1
通讯作者:
M. Kuroda;H. Sasamura;E. Kobayashi;R. Shimizu-Hirota;Y. Nakazato;M. Hayashi;T. Saruta
M. Kuroda;H. Sasamura;E. Kobayashi;R. Shimizu-Hirota;Y. Nakazato;M. Hayashi;T. Saruta
中科院分区:
医学4区
文献类型:
--
作者:
M. Kuroda;H. Sasamura;E. Kobayashi;R. Shimizu-Hirota;Y. Nakazato;M. Hayashi;T. Saruta

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最近的研究表明,细胞外基质的富含亮氨酸的小蛋白聚糖(SLRP)在调节生长因子的活性和调节胶原沉积中起着重要作用。在本研究中,我们检测了原发性肾小球疾病(微小改变疾病、IgA肾病和膜性肾病)患者肾小球中slrp的表达和尿免疫反应水平。方法对微小病变、IgA肾病和膜性肾病患者进行肾活检。用抗多糖和抗decorin抗体对新鲜冷冻样品进行免疫组化染色。采用间接ELISA法检测26例患者和8例正常人的尿蛋白多糖排泄量。结果在正常肾脏中,biglycan和decorin主要表达于肾内动脉和小管间质,仅在肾小球中有少量表达。在所有4例肾小球疾病患者中,这些蛋白多糖在肾小球疾病中的表达没有变化,疾病变化很小。在IgA肾病或膜性肾病的病例中,一些患者表现为biglycan或decorin的免疫染色轻微增加,但没有两种蛋白聚糖同时上调的迹象。为了进一步检测蛋白多糖表达的变化,我们对尿液样本进行了ELISA检测。尿多糖水平低于检测水平,但肾小球疾病患者尿decorin免疫反应性较高。尿decorin与肌酐清除率呈显著负相关。结论原发性肾小球疾病患者的slrp蛋白,biglycan和decorin的表达可能有明显变化。此外,尿decorin水平与肾功能之间的负相关关系支持了decorin可能参与人类肾功能障碍病理生理的假设。
AIMS Recent studies have suggested that small leucine-rich proteoglycans (SLRP) of the extracellular matrix play a major role in modulating the activity of growth factors and in regulating the deposition of collagens. In this study, the expression of the SLRPs biglycan and decorin in the glomeruli of patients with primary glomerular disease (minimal change disease, IgA nephropathy, and membranous nephropathy) and urine immunoreactive levels examined. METHODS Renal biopsy specimens were obtained from patients with minimal change disease, IgA nephropathy and membranous nephropathy. Immunohistochemical staining was performed on fresh-frozen samples using anti-biglycan and anti-decorin antibodies. Examination of urine proteoglycan excretion from a total of 26 patients and 8 normal volunteers was performed by indirect ELISA. RESULTS In normal kidney samples, biglycan and decorin expression was found predominantly in the intrarenal arteries and tubulointerstitium, with only minimal expression in the glomeruli. Glomerular expression of these proteoglycans in glomerular disease was unchanged in all of the 4 patients examined with minimal change disease. In the case of IgA nephropathy or membranous nephropathy, some of the patients showed minimally increased immunostaining of either biglycan or decorin, but there were no signs of simultaneous upregulation of both proteoglycans. To further examine the changes in proteoglycan expression, ELISA was performed on urine samples. Urine biglycan levels were below detection levels, but high values of urine decorin immunoreactivity were found in the patients with glomerular disease. A significant negative correlation was found between urine decorin and creatinine clearance. CONCLUSION These results suggest that distinct changes in the expression of the SLRPs biglycan and decorin may be seen in patients with primary glomerular disease. Moreover, the negative relationship between urine decorin levels and renal function supports the hypothesis that decorin may be involved in the pathophysiology of renal dysfunction in humans.