Different pattern of collagen cross-links in two sclerotic skin diseases:: Lipodermatosclerosis and circumscribed scleroderma
Different pattern of collagen cross-links in two sclerotic skin diseases:: Lipodermatosclerosis and circumscribed scleroderma
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DOI：
10.1046/j.0022-202x.2001.01414.x
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发表时间：
2001-08-01
影响因子：
6.5
通讯作者：
Scharffetter-Kochanek, K
中科院分区：
文献类型：
--
作者：
Brinckmann, J;Neess, CM;Scharffetter-Kochanek, K
胶原蛋白分子交联过程中的变化与细胞外基质生物力学稳定性的缺陷有关。皮肤纤维化的特征是吡啶增加，这是羟基赖氨酸醛衍生的交联，通常在健康皮肤中不存在。在这项研究中，我们分析了脂质皮肤硬化和局限性硬皮病中的交联，以解决除了吡啶增加外，目前表征的所有成熟交联是否在纤维化中增加的问题。由于补骨脂素加紫外线A治疗可改善局限性硬皮病纤维化斑块的临床情况，我们分析了沐浴后补骨脂素加紫外线A治疗后病变皮肤的交联含量。在局部硬皮病患者的皮肤中，成熟交联总数的增加被发现是由于吡啶类和脱氢组氨酸二羟甲基氨基葡萄糖的增加。组氨酸二羟基赖氨酸氨基亮氨酸的浓度不变。相比之下，在脂质皮肤硬化中，成熟交联的总数减少。这种减少是由于赖氨酸醛衍生的交联（脱氢组氨酸二羟化氨基葡萄糖和组氨酸二羟化氨基去亮氨酸）减少造成的，而吡啶的浓度增加。在9例局部硬皮病患者中，有6例在沐浴补骨脂素加紫外线A治疗后，发现吡啶碱含量降低，这可能反映了细胞外基质的重塑。我们的数据提供的证据表明，皮肤硬化要么与胶原蛋白每分子交联数量的增加有关，要么与形成的交联分子性质的变化有关。
Changes in the process of cross-linking of collagen molecules are associated with defects in the biomechanical stability of the extracellular matrix. Fibrosis of skin is characterized by an increase in pyridinolines, which are hydroxylysine aldehyde derived cross-links usually absent in healthy skin. In this study, we analyzed cross-links in lipodermatosclerosis and localized scleroderma to address the question whether all the mature cross-links currently characterized are increased in fibrosis in addition to the increase in pyridinolines. As psoralen plus ultraviolet A treatment leads to clinical improvement of fibrotic plaques in localized scleroderma we analyzed the cross-link content in lesional skin after bath psoralen plus ultraviolet A therapy. In skin from patients with localized scleroderma an increase in the total number of mature cross-links was found to be due to an increase in both pyridinolines and dehydro-histidinohydroxymerodesmosine. The concentration of histidinohydroxylysinonorleucine was unchanged. By contrast, the total number of mature cross-links was decreased in lipodermatosclerosis. This decrease was caused by a decrease of lysine aldehyde derived cross-links (dehydro-histidinohydroxymerodesmosine and histidinohydroxylysinonorleucine), whereas the concentration of pyridinolines increased. A decrease in the content of pyridinolines after bath psoralen plus ultraviolet A treatment was found in six out of nine patients with localized scleroderma, which might reflect a remodeling of the extracellular matrix. Our data provide evidence that sclerosis of skin is associated with either an increase in the number of cross-links per molecule of collagen or a change in the molecular nature of the cross-links formed.