Kuroda M, Sasamura H, Kobayashi E, Shimizu-Hirota R, Nakazato Y, Hayashi M, Saruta T
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Clin Nephrol. 2004 Jan;61(1):7-16. doi: 10.5414/cnp61007.
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.
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.
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.
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.
近期研究表明,细胞外基质中的富含亮氨酸小分子蛋白聚糖(SLRP)在调节生长因子活性和调控胶原蛋白沉积方面发挥着主要作用。在本研究中,检测了原发性肾小球疾病(微小病变肾病、IgA肾病和膜性肾病)患者肾小球中双糖链蛋白聚糖和核心蛋白聚糖这两种SLRP的表达情况以及尿液中的免疫反应水平。
获取微小病变肾病、IgA肾病和膜性肾病患者的肾活检标本。使用抗双糖链蛋白聚糖抗体和抗核心蛋白聚糖抗体对新鲜冷冻样本进行免疫组织化学染色。通过间接酶联免疫吸附测定法检测了总共26例患者和8名正常志愿者的尿液蛋白聚糖排泄情况。
在正常肾脏样本中,双糖链蛋白聚糖和核心蛋白聚糖的表达主要见于肾内动脉和肾小管间质,在肾小球中的表达极少。在所有4例接受检测的微小病变肾病患者中,这些蛋白聚糖在肾小球疾病中的肾小球表达未发生变化。在IgA肾病或膜性肾病患者中,部分患者双糖链蛋白聚糖或核心蛋白聚糖的免疫染色略有增加,但未出现两种蛋白聚糖同时上调的迹象。为进一步检测蛋白聚糖表达的变化,对尿液样本进行了酶联免疫吸附测定。尿液中双糖链蛋白聚糖水平低于检测限,但在肾小球疾病患者中发现尿液核心蛋白聚糖免疫反应性较高。尿液核心蛋白聚糖与肌酐清除率之间存在显著负相关。
这些结果表明,原发性肾小球疾病患者中可能会出现双糖链蛋白聚糖和核心蛋白聚糖这两种SLRP表达的明显变化。此外,尿液核心蛋白聚糖水平与肾功能之间的负相关支持了核心蛋白聚糖可能参与人类肾功能障碍病理生理过程的假说。