Tsujihata M, Miyake O, Yoshimura K, Kakimoto K, Takahara S, Okuyama A
Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Eur Urol. 2001 Oct;40(4):458-62. doi: 10.1159/000049816.
Fibronectin (FN: 230 kD) is a multifunctional alpha(2)-glycoprotein distributed throughout the extracellular matrix and body fluids. Recent studies have shown that a variety of molecules, including FN, inhibit the endocytosis of calcium oxalate (CaOx) crystals in vitro. We recently reported that FN was oversecreted from the renal tubular cells as a result of the stimulation of CaOx crystals, and inhibited the aggregation of CaOx crystals and the adhesion of CaOx crystals to the renal tubular cells. In the present study, we investigated the difference of FN content in urinary macromolecules (UMMs) between normal subjects and recurrent stone formers.
Urinary parameters in relation to urolithiasis of normal subjects and recurrent stone formers were measured. Proteins in extracted UMMs from urine of normal subjects and recurrent stone formers were measured with a BioRad protein assay, GAGs in each UMMs with a modified DMB assay and the FN content with the ELISA method.
In urinary parameters, citrate was significantly higher in urine from normal subjects (female) than normal subjects (male) or recurrent stone formers, and the other parameters showed no differences between each group. The protein concentrations in UMMs showed no differences between each group. Normal subjects (male and female) showed a significantly higher concentration of GAGs than recurrent stone formers (with and without silent stone). Compared with normal subjects and recurrent stone formers without silent stones, higher FN levels were found in recurrent stone formers with silent stones. Normal subjects showed a significantly higher concentration of FN than recurrent stone formers without silent stones. No difference in FN level was shown between normal subjects (male) and normal subjects (female).
Recurrent stone formers with silent stones showed a significantly higher concentration of FN in UMMs than normal subjects. This finding suggests that FN might be oversecreted from the renal tubular cells as a result of the stimulation of CaOx stones in vivo. Recurrent stone formers without silent stones showed a significantly lower concentration of FN in UMMs than normal subjects. From this finding it is suggested that FN might play a role as a potent inhibitor of CaOx urolithiasis in a clinical setting.
纤连蛋白（FN：230kD）是一种多功能α(2)-糖蛋白，分布于细胞外基质和体液中。最近的研究表明，包括FN在内的多种分子在体外可抑制草酸钙（CaOx）晶体的内吞作用。我们最近报道，由于CaOx晶体的刺激，肾小管细胞会过度分泌FN，并且FN可抑制CaOx晶体的聚集以及CaOx晶体与肾小管细胞的黏附。在本研究中，我们调查了正常受试者和复发性结石形成者尿大分子（UMMs）中FN含量的差异。
测量正常受试者和复发性结石形成者与尿路结石相关的尿液参数。采用BioRad蛋白测定法测量从正常受试者和复发性结石形成者尿液中提取的UMMs中的蛋白质，采用改良的DMB测定法测量各UMMs中的糖胺聚糖（GAGs），并采用ELISA法测量FN含量。
在尿液参数方面，正常受试者（女性）尿液中的柠檬酸盐显著高于正常受试者（男性）或复发性结石形成者，而其他参数在各组之间无差异。UMMs中的蛋白质浓度在各组之间无差异。正常受试者（男性和女性）的GAGs浓度显著高于复发性结石形成者（有或无静止结石）。与正常受试者和无静止结石的复发性结石形成者相比，有静止结石的复发性结石形成者的FN水平更高。正常受试者的FN浓度显著高于无静止结石的复发性结石形成者。正常受试者（男性）和正常受试者（女性）之间的FN水平无差异。
有静止结石的复发性结石形成者UMMs中的FN浓度显著高于正常受试者。这一发现表明，由于体内CaOx结石的刺激，FN可能从肾小管细胞中过度分泌。无静止结石的复发性结石形成者UMMs中的FN浓度显著低于正常受试者。从这一发现可以推测，在临床环境中，FN可能作为CaOx尿路结石的有效抑制剂发挥作用。
