Small proteoglycans of normal adult human kidney: distinct expression patterns of decorin, biglycan, fibromodulin, and lumican.
Small proteoglycans of normal adult human kidney: distinct expression patterns of decorin, biglycan, fibromodulin, and lumican.
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DOI：
10.1046/j.1523-1755.2000.00317.x
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发表时间：
2000-10
影响因子：
19.6
通讯作者：
L. Schaefer;L. Schaefer;L. Schaefer;H. Gröne;Igor Raslik;Igor Raslik;Igor Raslik;H. Robenek;H. Robenek;H. Robenek;J. Ugorcakova;J. Ugorcakova;J. Ugorcakova;S. Budny;S. Budny;S. Budny;R. Schaefer;R. M. Schaefer;R. M. Schaefer;H. Kresse;H. Kresse;H. Kresse
中科院分区：
文献类型：
--
作者：
L. Schaefer;L. Schaefer;L. Schaefer;H. Gröne;Igor Raslik;Igor Raslik;Igor Raslik;H. Robenek;H. Robenek;H. Robenek;J. Ugorcakova;J. Ugorcakova;J. Ugorcakova;S. Budny;S. Budny;S. Budny;R. Schaefer;R. M. Schaefer;R. M. Schaefer;H. Kresse;H. Kresse;H. Kresse
在富含亮氨酸的小蛋白聚糖家族的成员中，核心蛋白聚糖、双糖链蛋白聚糖和纤调蛋白已被认为是转化生长因子-β（TGF-β）活性的有效调节剂，从而在纤维化肾病的发病机制中起重要作用。此外，核心蛋白聚糖的表达影响p21 WAF 1/CIP 1的表达，这与肾脏肥大和增生有关。然而，尚未在正常成人肾皮质中研究过该蛋白聚糖家族的任何成员，因此不可能将疾病介导的其表达变化与体内正常情况联系起来。方法应用免疫组织化学和原位杂交技术，对正常成人肾皮质中的软骨素/硫酸皮肤素蛋白聚糖（核心蛋白聚糖和双糖链蛋白聚糖）和硫酸角质素蛋白聚糖（纤调素和光蛋白聚糖）进行研究。采用北方杂交和逆转录-聚合酶链反应（RT-PCR）方法检测其在肾小球中的表达。通过蛋白质印迹法测量随尿液的核心蛋白聚糖排泄。结果在离体肾小球的北方印迹中鉴定出两条核心蛋白聚糖和一条双糖链蛋白聚糖mRNA带。需要通过RT-PCR扩增来检测纤调蛋白和光蛋白聚糖的信号。所有四种蛋白聚糖优先表达在肾小管周围的积累肾间质。在系膜基质中有弱表达。双糖蛋白聚糖由肾小球内皮细胞表达，并与纤维调节蛋白一起合成并沉积在远端肾小管细胞和集合管中。免疫金标记表明肾小球基底膜中存在蛋白多糖，这被解释为肾小球滤过的结果。间接证据表明肾小球滤过后肾小管重摄取核心蛋白聚糖。结论成人肾脏不同细胞中四种小分子蛋白聚糖的表达模式不同。有人建议，这些蛋白聚糖可能有不同的病理生理作用，这取决于它们是否表达的系膜细胞，内皮细胞，上皮细胞，或细胞的tubuloacetitium。
BACKGROUND Among the members of the small leucine-rich proteoglycan family, decorin, biglycan, and fibromodulin have been proposed to be potent modulators of transforming growth factor-beta (TGF-beta) activity, thereby playing an important role in the pathogenesis of fibrotic kidney diseases. Furthermore, decorin expression influences the expression of p21WAF1/CIP1, which has been related to kidney hypertrophy and hyperplasia. However, none of the members of this proteoglycan family have been investigated in normal adult human kidney cortex, thus making it impossible to correlate disease-mediated alterations of their expression with the normal situation in vivo. METHODS The chondroitin/dermatan sulfate proteoglycans, decorin and biglycan, and the keratan sulfate proteoglycans, fibromodulin and lumican, were investigated in normal human adult renal cortex by immunohistochemistry on the light and electron microscopic level and by in situ hybridization. Northern blot and reverse transcription-polymerase chain reaction (RT-PCR) methods were used to get an estimate of their expression in isolated glomeruli. Decorin excretion with the urine was measured by Western blotting. RESULTS Two bands of decorin and a single band of biglycan mRNA were identified in Northern blots of isolated glomeruli. Amplification by RT-PCR was required to detect the signals for fibromodulin and lumican. All four proteoglycans were preferentially expressed in the renal interstitium with accumulations around tubules. Weak expression was found in the mesangial matrix. Biglycan was expressed by glomerular endothelial cells and, together with fibromodulin, was synthesized and deposited in distal tubular cells and collecting ducts. Immunogold labeling indicated the presence of the proteoglycans in the glomerular basement membrane, which was interpreted as a result of glomerular filtration. Indirect evidence suggested tubular reuptake of decorin after glomerular filtration. CONCLUSION The data indicate that the different cells of the adult human kidney are characterized by a distinct expression pattern of the four small proteoglycans. It is suggested that these proteoglycans may have distinct pathophysiological roles depending upon whether they are expressed by mesangial cells, endothelial cells, epithelial cells, or cells of the tubulointerstitium.