Tubular basement membrane change occurs pari passu with the development of cyst formation.
Tubular basement membrane change occurs pari passu with the development of cyst formation.
复制标题
管状基底膜的变化与囊肿形成的发展同时发生。
DOI：
10.1038/ki.1989.87
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发表时间：
1989
影响因子：
19.6
通讯作者：
Flouret,G
中科院分区：
文献类型：
--
作者：
Carone,FA;Hollenberg,PF;Nakamura,S;Punyarit,P;Glogowski,W;Flouret,G
肾小管基底膜的改变与囊肿的形成同步发生。我们以前的研究表明，2-氨基-4，5-二苯基噻唑盐酸盐（DPT）口服给药大鼠诱导尿液浓缩缺陷（1至2天内）和进行性，但可逆的，所有收集小管的囊性变化（4至8周之间突出）。囊性变化的特征是肾小管细胞和基底膜变化，包括细胞生物合成/分泌细胞器的改变，随后是基底膜增厚，硫酸化蛋白聚糖的从头合成显著减少（约50%），表明肾小管基底膜的合成改变在囊性疾病的发展中起作用。在本研究中，体内给予[14 C]-DPT后，通过HPLC分离出一种主要的尿液代谢物（> 70%），并通过气相色谱-质谱和NMR分析表征为2-氨基-4-羟基苯基-5-苯基噻唑，命名为苯酚II。合成了苯酚II，并将其口服给大鼠四天，以比较其与DPT的生物学效应。苯酚II诱导的浓缩能力和肾小管囊性转化的损害比DPT显着更大。在第5天，在苯酚II处理的动物中，基底膜内衬囊肿增厚数倍，并表现出钌红结合位点的广泛损失和紊乱，表明硫酸化蛋白聚糖（硫酸肝素蛋白聚糖）的损失。基底膜的改变与囊变的发生是同步的，强烈提示基底膜在PKD的发病机制中具有关键作用。研究结果支持PKD可能是由于一种或多种基底膜组分（硫酸化蛋白聚糖）的合成/降解缺陷导致肾小管形态发生缺陷的假设。
Renal tubular basement membrane change occurs pari passu with the development of cyst formation. Our previous studies have shown that 2-amino-4, 5-diphenyl thiazole hydrochloride (DPT) administered orally to rats induces a urine concentrating defect (within 1 to 2 days) and progressive, but reversible, cystic change of all collecting tubules (prominent between 4 and 8 weeks). Cystic change was characterized by tubular cell and basement membrane changes consisting of alterations in cellular biosynthetic/secretory organelles, followed by thickening of the basement membrane with marked reduction (∼50%) of the de novo synthesis of sulfated proteoglycans, suggesting that altered synthesis of tubular basement membrane plays a role in the development of cystic disease. In this study, following the administration of [14C]-DPT in vivo, a major urinary metabolite (> 70%) was isolated by HPLC and characterized by gas chromatographic-mass spectral and NMR analyses as 2-amino-4-hydroxyphenyl-5 phenyl thiazole, designated phenol II. Phenol II was synthesized and administered orally to rats for four days to compare its biological effects with DPT. Phenol II induced a significantly greater impairment of concentrating ability and tubular cystic transformation than DPT. At day 5, in phenol II treated animals, basement membranes lining cysts were thickened several-fold and exhibited extensive loss and disorder of ruthenium red binding sites, indicative of loss of sulfated proteoglycans (heparin sulfate proteoglycan). The basement membrane changes occurred in tandem with the development of cystic transformation and strongly suggests that the basement membrane has a key role in the pathogenesis of PKD. The findings support the hypothesis that PKD may be due to a defect in the synthesis/degradation of one or more basement membrane components (sulfated proteoglycans) resulting in faulty tubular morphogenesis.