Bauer E A, Seltzer J L, Eisen A Z
J Am Acad Dermatol. 1982 Apr;6(4 Pt 2 Suppl):603-7. doi: 10.1016/s0190-9622(82)70049-0.
The effects of a variety of retinoids on collagenase and gelatinase expression have been examined in skin fibroblast cultures derived from normal volunteers and from patients with the hereditary blistering disorder, recessive dystrophic epidermolysis bullosa. Both 13-cis- and all-trans-retinoic acid were effective inhibitors of collagenase production in both cell types. In the case of collagenase, the inhibition of collagenase activity was paralleled by a reduction in immunoreactive enzyme protein, suggesting that these retinoids act by inhibiting synthesis and/or secretion of the enzyme. Retinoic acid also inhibited production of the second enzyme in the collagen degradative pathway, gelatinase. In this case, the decrease in gelatinase activity was equal to or slightly greater than the achieved in collagenase expression. The observation that certain retinoids modulate the two crucial enzymes in the degradation of collagen in the skin suggests that they might be useful therapeutic agents in recessive dystrophic epidermolysis bullosa, a disease in which the pathogenesis of blistering is in part related to connective tissue destruction.
在源自正常志愿者以及患有遗传性水疱病（隐性营养不良型大疱性表皮松解症）患者的皮肤成纤维细胞培养物中，研究了多种类视黄醇对胶原酶和明胶酶表达的影响。13 - 顺式视黄酸和全反式视黄酸对这两种细胞类型中的胶原酶产生均为有效的抑制剂。就胶原酶而言，胶原酶活性的抑制与免疫反应性酶蛋白的减少相平行，这表明这些类视黄醇通过抑制该酶的合成和/或分泌起作用。视黄酸还抑制了胶原降解途径中的第二种酶——明胶酶的产生。在这种情况下，明胶酶活性的降低等于或略大于胶原酶表达中的降低。某些类视黄醇可调节皮肤中胶原降解的两种关键酶这一观察结果表明，它们可能是隐性营养不良型大疱性表皮松解症的有用治疗药物，在该疾病中，水疱形成的发病机制部分与结缔组织破坏有关。
