Colchicine-induced modulation of collagenase in human skin fibroblast cultures. II. A probe for defective regulation in epidermolysis bullosa.
Colchicine-induced modulation of collagenase in human skin fibroblast cultures. II. A probe for defective regulation in epidermolysis bullosa.
复制标题
秋水仙碱诱导人皮肤成纤维细胞培养物中胶原酶的调节。
DOI：
10.1111/1523-1747.ep12530308
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
Esterly,NB
中科院分区：
文献类型：
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作者：
Bauer,EA;Valle,KJ;Esterly,NB
向正常人皮肤成纤维细胞中添加秋水仙碱可显著刺激胶原酶。由于这一发现暗示了微管系统在调节正常胶原酶合成中的作用，我们使用秋水仙碱作为大疱性表皮松解症中胶原酶畸变的探针。在从显性单纯型、显性营养不良型和隐性叶状型大疱表皮松解症的成纤维细胞培养中，10 - 6毫升秋水仙碱使培养基中的胶原酶增加了约2倍，生物合成研究表明，这一发现可归因于酶蛋白的合成增强。在典型的隐性营养不良大泡性表皮松解症（一种以胶原酶合成过度为特征的疾病）的病例中，尽管基线合成率升高，但也可以刺激成纤维细胞产生额外的胶原酶。相比之下，从一名隐性大疱性表皮松解症患者分离的成纤维细胞对秋水仙碱浓度高达5 × 10−6m的刺激作用具有抵抗力。在缺乏秋水仙碱的情况下，该患者细胞（称为REBc -）的胶原酶合成是正常对照的3-4倍，这表明正常细胞中被秋水仙碱取消（或刺激）的尚未确定的细胞功能可能在这些REBc -细胞中受到遗传损害。尽管对秋水仙碱有抗性，表现为不能刺激胶原酶，但微管功能的总体参数，如细胞复制，是完整的。在表型上，该患者有一种介于典型隐性营养不良和隐性叶状畸形之间的大疱性表皮松解。虽然实验诱导的水疱位于透明层，但也观察到锚定原纤维发育不全。这些发现，加上胶原酶合成的显著增加，提示该患者可能是两种大疱性表皮松解症的复合杂合子，秋水仙碱可能有助于确定其他此类患者。
The addition colchicine to cultures of normal human skin fibroblasts produces a significant stimulation of collagenase. Because this finding implies a role for the microtubule system in the regulation of normal collagenase synthesis, we have used colchicine as a probe for aberrations in this enzyme in epidermolysis bullosa. In fibroblast cultures from the dominant simplex, dominant dystrophic, and recessive letalis forms of epidermolysis bullosa, 10−6mcolchicine produced approximately a 2-fold increase in collagenase in the culture medium, a finding shown by biosynthetic studies to be attributable to enhanced synthesis of enzyme protein. In the case of typical recessive dystrophic epidermolysis bullosa, a disease characterized by excessive collagenase synthesis, the fibroblasts could also be stimulated to produce additional collagenase, despite having elevated baseline synthetic rates. In contrast, fibroblasts isolated from one recessive epidermolysis bullosa patient were resistant to the stimulatory effects of colchicine in concentrations up to 5 × 10−6m. In the absence of colchicine, collagenase synthesis in this patient's cells (termed REBc−) was 3–4 times that of normal controls, suggesting that the as yet undefined cellular function that is abrogated (or stimulated) by colchicine in normal cells may have been genetically impaired in these REBc−cells. Despite the resistance to colchicine, as manifested by the failure to stimulate collagenase, gross parameters of microtubular function, such as cell replication, were intact. Phenotypically, this patient had a form of epidermolysis bullosa intermediate between typical recessive dystrophic and recessive letalis forms of the disease. Although an experimentally induced blister was located in the lamina lucida, hypoplastic anchoring fibrils were also observed. These findings, in addition to the marked increase in collagenase synthesis, suggest the possibility that this patient may represent a compound heterozygote of two forms of epidermolysis bullosa and that colchicine may be useful in defining other such patients.