Parikh D H, Leibl M, Tam P K, Edgar D
Institute of Child Health, University of Liverpool, England.
J Pediatr Surg. 1995 Dec;30(12):1687-93. doi: 10.1016/0022-3468(95)90453-0.
Hirschsprung's disease (congenital colonic aganglionosis) is associated with abnormalities in the distributions and amounts of basement membrane and other extracellular matrix components in the human gut. The authors have investigated the possible significance of nidogen in Hirschsprung's disease, because this glycoprotein is necessary for the formation of ternary complexes with the other basement membrane components, laminin and collagen type IV, and thus may contribute the pathology of the disease. Increased nidogen immunoreactivity in the smooth muscle basement membranes and muscularis mucosae of the distal aganglionic zone in Hirschsprung's bowel was observed, the nidogen immunoreactivity demonstrating that the thickness of the muscularis mucosae was increased in this region. However, steady-state nidogen mRNA levels were found to be significantly lower in both proximal and distal Hirschsprung's bowel (relative to controls). In contrast, no significant differences were observed in the steady-state levels of the mRNAs coding for laminin subunits. These results indicate that although abnormalities in the amount or distribution of nidogen may contribute to the abnormalities seen in the extracellular matrix in Hirschsprung's disease, the levels of expression of the genes coding for either nidogen or laminin are unlikely to be primarily responsible for the lesions.
先天性巨结肠（先天性结肠神经节细胞缺失症）与人肠道中基底膜及其他细胞外基质成分的分布和数量异常有关。作者研究了巢蛋白在先天性巨结肠中的潜在意义，因为这种糖蛋白对于与其他基底膜成分（层粘连蛋白和IV型胶原）形成三元复合物是必需的，因此可能与该疾病的病理过程有关。在先天性巨结肠肠段远端无神经节区的平滑肌基底膜和黏膜肌层中观察到巢蛋白免疫反应性增加，巢蛋白免疫反应性表明该区域黏膜肌层厚度增加。然而，发现先天性巨结肠近端和远端肠段的巢蛋白稳态mRNA水平均显著低于对照组（相对于对照）。相比之下，编码层粘连蛋白亚基的mRNA稳态水平未观察到显著差异。这些结果表明，尽管巢蛋白数量或分布异常可能导致先天性巨结肠中细胞外基质出现异常，但编码巢蛋白或层粘连蛋白的基因表达水平不太可能是病变的主要原因。
