Schäfer K, Bader M, Gretz N, Oberbäumer I, Bachmann S
Institut für Anatomie und Zellbiologie 1, Universität Heidelberg, FRG.
Exp Nephrol. 1994 May-Jun;2(3):190-5.
Changes of extracellular matrix are involved in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). The relationship between epithelial changes and extracellular matrix production was studied in a new rat model (Han:SPRD/cy+) at an early phase of cystogenesis. Messenger RNA expression of the alpha 1(IV)-chain of collagen type IV, the main structural component of basement membrane, was localized by in situ hybridization. The presence of collagen IV-protein was shown by immunohistochemistry. At an initial stage, cysts were lined with normal-appearing epithelium except for focal zones of less differentiated cells exhibiting strong collagen alpha 1(IV) mRNA expression and a thickened basement membrane. In these zones, an increase in cell number (2.39-fold) per unit epithelial area indicated hyperplastic growth. Conspicuously, these zones were found at 'bottleneck'-like transitions from normal-size tubules to cystic expansions. Intermediate stages of cysts showed more prominent extracellular matrix deposits and an overall maximally enhanced collagen IV mRNA expression, whereas terminal stages were lined with a flat, simplified epithelium and exhibited moderate collagen IV expression. We suggest that focally enhanced expression of collagen IV in the tubular epithelium and surrounding interstitium of Han:SPRD/cy+ rat kidney is initially involved in cyst development.
细胞外基质的变化参与常染色体显性多囊肾病（ADPKD）的发病机制。在一种新的大鼠模型（Han:SPRD/cy+）囊肿形成的早期阶段，研究了上皮细胞变化与细胞外基质产生之间的关系。通过原位杂交对基底膜的主要结构成分IV型胶原α1链的信使核糖核酸表达进行定位。通过免疫组织化学显示IV型胶原蛋白的存在。在初始阶段，囊肿内衬外观正常的上皮细胞，除了局部区域有分化程度较低的细胞，这些细胞表现出强烈的胶原α1(IV)信使核糖核酸表达和增厚的基底膜。在这些区域，每单位上皮面积的细胞数量增加（2.39倍）表明存在增生性生长。值得注意的是，这些区域出现在从正常大小的肾小管到囊性扩张的“瓶颈”样过渡处。囊肿的中间阶段显示出更明显的细胞外基质沉积和总体上最大程度增强的IV型胶原信使核糖核酸表达，而终末阶段则内衬扁平、简化的上皮细胞，并表现出中等程度的IV型胶原表达。我们认为，Han:SPRD/cy+大鼠肾脏的肾小管上皮细胞和周围间质中IV型胶原的局部增强表达最初参与囊肿的发展。
