Sato T, Nomura K, Hashimoto I
Department of Dermatology, Hirosaki University School of Medicine, Japan.
Arch Dermatol Res. 1995;287(5):428-33. doi: 10.1007/BF00373423.
Collagenase and stromelysin expression in recessive dystrophic epidermolysis bullosa (RDEB) was studied at both the protein and the gene expression levels in fibroblast cultures. The amount of enzyme protein in the culture medium, as determined using a specific enzyme assay, showed a 9.7-fold increase in collagenase and a 2.7-fold increase in stromelysin in RDEB fibroblasts (n = 4 patients) compared with controls (n = 3 subjects with normal skin). Collagenase activity was extremely high in all RDEB fibroblasts. Gene expression, as assessed by Northern blot hybridization, was increased in two sets of RDEB fibroblasts with respect to collagenase, and in two other sets of RDEB fibroblasts with respect to stromelysin. The effect of interleukin-1 alpha (IL-1 alpha) on metalloproteinase expression was also examined. The results revealed that: 1) collagenase and stromelysin expression was variably increased at both the protein and the gene expression levels in RDEB fibroblasts; (2) the gene expression level did not always reflect the corresponding protein level; and (3) IL-1 alpha produced a differential effect on collagenase and stromelysin expression. Although the causative gene for RDEB is a type VII collagen, the abnormal expression of collagenase and/or stromelysin is still important in considering the pathophysiology of RDEB.
在成纤维细胞培养物中，我们从蛋白质和基因表达水平研究了隐性营养不良性大疱性表皮松解症（RDEB）中胶原酶和基质溶解素的表达。使用特定的酶测定法测定培养基中的酶蛋白量，结果显示，与对照组（n = 3名皮肤正常的受试者）相比，RDEB成纤维细胞（n = 4例患者）中的胶原酶增加了9.7倍，基质溶解素增加了2.7倍。所有RDEB成纤维细胞中的胶原酶活性都极高。通过Northern印迹杂交评估的基因表达，在两组RDEB成纤维细胞中，胶原酶表达增加，在另外两组RDEB成纤维细胞中，基质溶解素表达增加。我们还研究了白细胞介素-1α（IL-1α）对金属蛋白酶表达的影响。结果显示：1）RDEB成纤维细胞中，胶原酶和基质溶解素在蛋白质和基因表达水平上均有不同程度的增加；（2）基因表达水平并不总是反映相应的蛋白质水平；（3）IL-1α对胶原酶和基质溶解素的表达产生了不同的影响。虽然RDEB的致病基因是VII型胶原蛋白，但在考虑RDEB的病理生理学过程中，胶原酶和/或基质溶解素的异常表达仍然很重要。
