Ebihara I, Killen P D, Laurie G W, Huang T, Yamada Y, Martin G R, Brown K S
Laboratory of Developmental Biology and Anomalies, National Institute of Dental Research, Bethesda, Maryland.
Lab Invest. 1988 Mar;58(3):262-9.
Basement membranes surround the renal tubules and have been shown to limit their distension in vitro. Therefore, it has been postulated that a defect in a basement membrane component(s) underlies the pathogenesis of polycystic kidney disease. Here we have studied a murine model of congenital polycystic kidney disease and found by immunohistology, that the components of the peri-cyst basement membrane appeared to diminish with time. We also measured mRNA levels for collagen IV and laminin, and found a different pattern than in the normal mouse kidney. In normal kidneys, mRNA levels for the B1 and B2 chains of laminin were maximal at birth, and at 1 week for the alpha 1(IV) chain of collagen IV. With all three chains, the levels then rapidly declined. In contrast, mRNA for the alpha 1(IV) chain in congenital polycystic kidneys was half normal 1 week after birth and then increased. Laminin B1 and B2 chain mRNA's were 80% of normal at 1 week but were maintained at that level. As a control, beta-actin mRNA was examined and found to remain constant in both normal and diseased kidneys. In situ hybridization of cRNA probes for the alpha 1(IV) chain confirmed that cells associated with cysts were the principal source of expression of these basement membrane mRNAs. Thus, there exists an abnormal regulation of basement membrane gene expression in congenital polycystic kidney disease. The first stage is characterized by reduced levels of expression. In the second stage, the levels are abnormally high, perhaps representing a compensatory synthesis of basement membrane as cysts enlarge.
基底膜围绕肾小管，并且已证实在体外能限制肾小管的扩张。因此，有人推测多囊肾病的发病机制是基底膜成分存在缺陷。在此，我们研究了先天性多囊肾病的小鼠模型，通过免疫组织学发现，囊肿周围基底膜的成分似乎随时间减少。我们还检测了IV型胶原和层粘连蛋白的mRNA水平，发现其模式与正常小鼠肾脏不同。在正常肾脏中，层粘连蛋白B1和B2链的mRNA水平在出生时最高，IV型胶原α1(IV)链的mRNA水平在出生后1周最高。之后，这三条链的水平均迅速下降。相比之下，先天性多囊肾中IV型胶原α1(IV)链的mRNA在出生后1周时为正常水平的一半，随后升高。层粘连蛋白B1和B2链的mRNA在出生后1周时为正常水平的80%，并维持在该水平。作为对照，检测了β-肌动蛋白mRNA，发现其在正常和患病肾脏中均保持恒定。针对IV型胶原α1(IV)链的cRNA探针原位杂交证实，与囊肿相关的细胞是这些基底膜mRNA表达的主要来源。因此，先天性多囊肾病存在基底膜基因表达的异常调控。第一阶段的特征是表达水平降低。在第二阶段，水平异常升高，这可能代表随着囊肿增大，基底膜的代偿性合成。
