Tanaka Y, Tsuchiya K, Mochizuki T, Aikawa E, Nihei H
Department of Medicine IV, Tokyo Women's Medical University, Tokyo, Japan.
Nihon Jinzo Gakkai Shi. 2000 Oct;42(7):583-90.
A second gene responsible for polycystic kidney disease(PKD) has been identified recently, and an antisera(YCC2) against this gene's product, polycystin 2, has been generated. In the present study, we investigated the normal distribution of polycystin 2 in human adult kidneys and analyzed the expression of polycystin 2 in the cystic tubules of kidneys from patients with PKD and acquired cystic disease of the kidney(ACDK). The expression of polycystin 2 in normal regions of resected human kidneys, 4 cases of autosomal dominant polycystic kidney disease(ADPKD) and 4 cases of ACDK was examined by immunohistochemically staining the specimens with a polyclonal antibody specific to the C-terminal region of polycystin 2. This region is specific to polycystin 2 and does not crossreact with polycystin 1. In normal kidneys, prominent expression of polycystin 2 was observed in the distal tubules. A faint level of expression was detected in the proximal tubules, and the glomerulus and vessels were almost negative for expression. In the cystic kidneys of ADPKD patients, 68.7% of the cystic tubules stained positively for YCC2, although partial staining was seen in 41.2% of the positive cystic tubules. Although the genetic background of the samples is unknown, the co-existence of positive and negative cysts suggest that a "two-hit" hypothesis is feasible and that the mutations are likely to be missense or in frame changes. In ACDK cysts, YCC2-positive staining was prominent in small cysts (less than 0.5 mm in diameter), which were also positive for DBA, a marker for distal tubules. In contrast, larger cysts of more than 0.5 mm in diameter which stained positive for a proximal tubule marker, Lotus T, tended to be less positively stained for YCC2. Overall, 94.5% of the cysts stained positive for YCC2, which is a much higher rate than that of PKD cysts. These results suggest that ACDK cysts may be generated by a different mechanism from that of PKD cysts.
最近已鉴定出第二种导致多囊肾病（PKD）的基因，并制备了针对该基因产物多囊蛋白2的抗血清（YCC2）。在本研究中，我们调查了多囊蛋白2在成人肾脏中的正常分布，并分析了多囊蛋白2在PKD患者和获得性肾囊肿病（ACDK）患者肾脏的囊性小管中的表达。通过用针对多囊蛋白2 C末端区域的多克隆抗体对标本进行免疫组织化学染色，检测了4例常染色体显性多囊肾病（ADPKD）和4例ACDK患者切除的人肾脏正常区域中多囊蛋白2的表达。该区域对多囊蛋白2具有特异性，且不与多囊蛋白1发生交叉反应。在正常肾脏中，在远端小管中观察到多囊蛋白2的显著表达。在近端小管中检测到微弱的表达水平，而肾小球和血管几乎无表达。在ADPKD患者的囊性肾脏中，68.7%的囊性小管YCC2染色呈阳性，尽管在41.2%的阳性囊性小管中可见部分染色。尽管样本的遗传背景未知，但阳性和阴性囊肿的共存表明“二次打击”假说是可行的，且突变可能是错义突变或框内改变。在ACDK囊肿中，YCC2阳性染色在小囊肿（直径小于0.5mm）中很突出，这些小囊肿对远端小管标记物DBA也呈阳性。相反，直径大于0.5mm且对近端小管标记物莲花凝集素T呈阳性的较大囊肿，YCC2染色往往较弱。总体而言，94.5%的囊肿YCC2染色呈阳性，这一比例远高于PKD囊肿。这些结果表明，ACDK囊肿可能由与PKD囊肿不同的机制产生。
