Calvet J P
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City.
Kidney Int. 1993 Jan;43(1):101-8. doi: 10.1038/ki.1993.17.
Polycystic kidney disease (PKD) is inherited as a dominant or recessive trait or can be provoked by environmental factors. The disease is characterized by the growth of large epithelial-lined cysts derived from the nephrons and collecting ducts of affected kidneys. Cysts are thought to initiate as small dilations in renal tubules, which then expand into fluid-filled cavities of relatively large size. Cyst formation appears to involve increased cell proliferation, reversal of tubular epithelial polarity, and epithelial fluid secretion. In addition, a number of pronounced extracellular matrix changes have been found in the cystic kidneys of several animal models and in human autosomal dominant PKD. These abnormalities include thickened, laminated basement membrane, increased expression of alpha 1 type IV collagen and laminins B1 and B2, and changes in heparan sulfate proteoglycan and fibronectin. Some of these changes can also be seen in vitro, reflecting intrinsic abnormalities, and may be associated with abnormal tubular morphogenesis early in cyst formation as well as later in cyst expansion. We have been investigating gene expression in the C57BL/6J-cpk mouse, which has an autosomal recessive form of PKD, to determine the genetic basis of the abnormal tubule cell growth and morphology manifested during cyst formation.(ABSTRACT TRUNCATED AT 250 WORDS)
多囊肾病（PKD）以显性或隐性性状遗传，也可由环境因素诱发。该疾病的特征是在受影响肾脏的肾单位和集合管中形成大量内衬上皮的囊肿。囊肿被认为起始于肾小管中的小扩张，然后扩展为相对较大的充满液体的腔。囊肿形成似乎涉及细胞增殖增加、肾小管上皮极性逆转和上皮液体分泌。此外，在几种动物模型的多囊肾以及人类常染色体显性PKD的囊肿肾中发现了许多明显的细胞外基质变化。这些异常包括增厚的分层基底膜、α1IV型胶原以及层粘连蛋白B1和B2的表达增加，以及硫酸乙酰肝素蛋白聚糖和纤连蛋白的变化。其中一些变化在体外也可见，反映了内在异常，并且可能与囊肿形成早期以及后期囊肿扩张过程中的肾小管形态异常有关。我们一直在研究具有常染色体隐性形式PKD的C57BL/6J-cpk小鼠中的基因表达，以确定囊肿形成过程中表现出的肾小管细胞生长和形态异常的遗传基础。（摘要截短于250字）
