Generalized dominant epidermolysis bullosa simplex: decreased activity of a gelatinolytic protease in cultured fibroblasts as a phenotypic marker.
Generalized dominant epidermolysis bullosa simplex: decreased activity of a gelatinolytic protease in cultured fibroblasts as a phenotypic marker.
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广泛性显性单纯性大疱性表皮松解症：作为表型标记的培养成纤维细胞中明胶分解蛋白酶的活性降低。
DOI：
10.1111/1523-1747.ep12523269
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
Bauer,EA
中科院分区：
文献类型：
--
作者：
Sanchez,G;Seltzer,JL;Eisen,AZ;Stapler,P;Bauer,EA
为了表征与各种形式的大疱性表皮病（EB）相关的生化特征，我们使用皮肤成纤维细胞培养来测量明胶特异性中性金属蛋白酶。与正常培养物相比，来自3名Koebner型泛发性显性单纯EB病（DEBS-K）患者的细胞培养物中这种明胶酶的水平降低了7倍（p < 0.00 1）。这种特性的特异性表现在几个方面。细胞的生长动力学和总蛋白合成没有改变。乳酸脱氢酶（一种细胞质酶）的活性也没有改变，表明细胞的完整性没有受到损害。明胶酶活性的降低是广义DEBS-K的特异性，因为隐性营养不良型EB、隐性交界型EB、显性营养不良型EB和第二种遗传类型的DEBS的培养物都没有显示出这种缺陷。然而，由于它已被建议，DEBS-K和DEBS的本地化形式，韦伯-Cockayne型（DEBS-WC），可能代表不同严重程度的等位基因突变，我们测量了明胶酶活性的细胞培养物中的13例这种类型的患者。水平显示出双相分离，其中13个值中有7个等于或大于对照细胞的平均活性。其余6例患者的培养物低于平均对照值> 1 SD，接近于在全身性DEBS-K患者中观察到的培养物。这些研究表明，明胶分解活性的降低是DEBS-K的标志，DEBS-K和DEBS-WC可能是密切相关的遗传性疾病，其中明胶分解蛋白酶的缺陷代表了DEBS基因的多效性效应或与DEBS基因遗传连锁。
To characterize biochemical traits associated with various forms of epidermolysis bullosa (EB), we used skin fibroblast cultures to measure a gelatin-specific neutral metalloprotease. Compared to normal cultures, levels of this gelatinase were 7-fold decreased in cell cultures from 3 patients from 3 kindreds with generalized dominant EB simplex of the Koebner type (DEBS-K) (p < 0.00 1). The specificity of this trait was shown in several ways. The growth kinetics and total protein synthesis of the cells were unaltered. The activity of lactic dehydrogenase, a cytoplasmic enzyme, was also unaltered, indicating the integrity of the cells was not compromised. The decrease in gelatinase activity is specific for generalized DEBS-K, since cultures from recessive dystrophic EB, recessive junctional EB, dominant dystrophic EB, and a second genetic type of DEBS all fail to show this defect. However, since it has been suggested that DEBS-K and the localized form of DEBS, the Weber-Cockayne type (DEBS-WC), may represent allelic mutations of varying severity, we measured gelatinase activity in cell cultures of 13 patients of this type. The levels displayed a biphasic segregation in which 7 of 13 values were equal to, or greater than, the mean activity of control cells. Cultures from the remain- ing 6 patients were> 1 SD below the mean control value and approximated those seen in the generalized DEBS-K patients. These studies suggest that the decrease in gelatinolytic activity is a marker for DEBS-K and that DEBS-K and DEBS-WC may be closely related genetic disorders in which the defect in gelatinolytic protease represents a pleiotropic effect of the gene for DEBS or is genetically linked to the DEBS gene.