Giro M G, Oikarinen A I, Oikarinen H, Sephel G, Uitto J, Davidson J M
J Clin Invest. 1985 Feb;75(2):672-8. doi: 10.1172/JCI111746.
Atrophoderma is a rare dermal disorder characterized by a patchy distribution of areas apparently devoid of elastic fibers. Skin fibroblast cultures were established from the normal and affected dermis of a patient with this disorder. Human tropoelastin was identified in culture medium by use of electroblotting and anti-elastin antisera. An enzyme-linked immunosorbent assay was used to establish that significantly less elastin accumulated in the media of cultured cells from lesional fibroblasts over a 3-d period. Since elastin biosynthesis in most tissues is under pretranslational control, molecular hybridization to a nick-translated genomic elastin probe was performed; however, elastin messenger RNA levels were equivalent in both cell strains. Both strains produced less elastin than did normal skin fibroblasts. Extracellular proteolysis of elastin was evaluated as a possible mechanism. Elastase activity was increased and porcine tropoelastin was degraded four times faster, on a per-cell basis, in lesional fibroblast cultures than in cells derived from an unaffected site. The two cell strains exhibited no significant differences in collagen production or collagenase activity. These results are the first demonstration of elastin production by cultured human skin fibroblasts, and they suggest that the primary defect in atrophoderma may be a result of enhanced degradation of newly synthesized elastin precursors.
萎缩性皮病是一种罕见的皮肤疾病，其特征为皮肤区域呈斑片状分布，明显缺乏弹性纤维。从一名患有这种疾病的患者的正常和病变真皮中建立了皮肤成纤维细胞培养物。通过使用电印迹法和抗弹性蛋白抗血清在培养基中鉴定出了人原弹性蛋白。使用酶联免疫吸附测定法确定，在3天的时间内，来自病变成纤维细胞的培养细胞培养基中积累的弹性蛋白明显较少。由于大多数组织中的弹性蛋白生物合成处于翻译前控制之下，因此对缺口平移的基因组弹性蛋白探针进行了分子杂交；然而，两种细胞株中的弹性蛋白信使核糖核酸水平相当。两种细胞株产生的弹性蛋白均少于正常皮肤成纤维细胞。评估了弹性蛋白的细胞外蛋白水解作为一种可能的机制。在病变成纤维细胞培养物中，弹性蛋白酶活性增加，每细胞基础上猪原弹性蛋白的降解速度比来自未受影响部位的细胞快四倍。两种细胞株在胶原蛋白产生或胶原酶活性方面没有显著差异。这些结果首次证明了培养的人皮肤成纤维细胞能够产生弹性蛋白，并且表明萎缩性皮病的主要缺陷可能是新合成的弹性蛋白前体降解增强的结果。
