Moy L S, Moy R L, Matsuoka L Y, Ohta A, Uitto J
J Am Acad Dermatol. 1987 Jun;16(6):1193-201. doi: 10.1016/s0190-9622(87)70157-1.
Lipoid proteinosis, a rare autosomal recessive disease, is histologically characterized by deposition of hyalinlike material in the dermis. In this study the pathologic processes of lipoid proteinosis were evaluated by ultrastructural and biochemical analysis of skin and cultured fibroblasts from a patient with classic features of the disease. Transmission electron microscopy revealed the presence of hyalinlike material with a granular appearance interspersed between collagen fibers. Immediately surrounding the blood vessel walls, there was reduplication of basal laminae in an "onionskin" arrangement. The fibroblastic cells in the affected dermis contained peculiar cytoplasmic inclusions. Biochemical studies with the cultured fibroblasts showed that the total synthesis of extracellular matrix components, as detected by the synthesis of radioactive hydroxyproline or the incorporation of 35SO4(2-) and [3H]glucosamine into macromolecules, was not altered in lipoid proteinosis. However, the relative expression of type I and type III procollagen genes, as detected by molecular hybridizations with pro-alpha 1(I) and pro-alpha 1(III) procollagen complementary deoxyribonucleic acid probes, was markedly altered in cultured fibroblasts. Specifically, the type I procollagen messenger ribonucleic acid (mRNA) levels were significantly reduced, resulting in a decreased type I/III procollagen mRNA ratio. Furthermore, the replicative capacity of lipoid proteinosis fibroblasts, as detected by the incorporation of radioactive thymidine, was reduced. Thus the skin fibroblasts from lipoid proteinosis demonstrate ultrastructural changes, as well as alterations in their phenotypic characteristics, and these changes may have relevance to the pathologic processes of this systemic disease affecting the skin and other organs.
类脂蛋白沉积症是一种罕见的常染色体隐性疾病，其组织学特征为真皮中透明样物质的沉积。在本研究中，通过对一名具有该疾病典型特征患者的皮肤和培养的成纤维细胞进行超微结构和生化分析，评估了类脂蛋白沉积症的病理过程。透射电子显微镜显示，在胶原纤维之间散布着具有颗粒外观的透明样物质。紧邻血管壁处，基底膜呈“洋葱皮”样排列重复。受累真皮中的成纤维细胞含有特殊的胞质内含物。对培养的成纤维细胞进行的生化研究表明，通过放射性羟脯氨酸的合成或35SO4(2-)和[3H]葡萄糖胺掺入大分子来检测，类脂蛋白沉积症中细胞外基质成分的总合成未发生改变。然而，通过与原α1(I)和原α1(III)前胶原互补脱氧核糖核酸探针进行分子杂交检测，I型和III型前胶原基因的相对表达在培养的成纤维细胞中发生了显著改变。具体而言，I型前胶原信使核糖核酸(mRNA)水平显著降低，导致I/III型前胶原mRNA比值下降。此外，通过放射性胸苷掺入检测，类脂蛋白沉积症成纤维细胞的复制能力降低。因此，类脂蛋白沉积症患者的皮肤成纤维细胞表现出超微结构变化以及表型特征的改变，这些变化可能与这种影响皮肤和其他器官的全身性疾病的病理过程相关。
