CONTROL OF COLLAGENASE IN HUMAN FIBROBLAST CULTURES

胶原酶，一种能够降解天然胶原蛋白的酶，对 在调节正常和正常的胶原重塑中起重要作用 病态的环境。对监管机制的理解 为胶原酶的体外表达提供了体内的洞察力 这些酶在皮肤病中的重要性。因此，这些研究 胶原酶和潜在的生理调节剂的作用 胶原酶的表达，如内源性基因产物本身， 类固醇激素和/或细胞-细胞相互作用的产物。这些 研究将与使用无细胞翻译的研究相关联 胶原酶决定原发胶原酶基因的性质 产品(S)，并确定是否调节胶原酶的表达 完整的细胞通过可翻译的信使核糖核酸的变化来反映。这些 将以正常生物合成调节的研究为基础。 用于定义导致增强合成的缺陷的性质 隐性营养不良性表皮松解症中胶原酶的异常形态 布洛萨。在这里，将使用生物合成和制备方法来 描述调节性缺陷和可能的突变 前胶原酶(S)和建立某些潜在的治疗 药理药剂。此外，我们还将研究基因的特异性 胶原酶的合成和/或结构有任何异常。这个 这些研究的生物学意义不仅仅在于定义正常 胶原蛋白降解的调节机制也要发展得准确 狂犬病的体外标志物和合理的治疗方式 遗传性皮肤病。

Collagenases, enzymes capable of degrading native collagen, are critically important in mediating the remodeling of collagen in both normal and pathologic circumstances. An understanding of the regulatory mechanisms for colagenase expression in vitro should provide insight into the in vivo importance of these enzymes in cutaneous dieases. Thus, these studies collagenese and to examine the effects of potential physiologic modulators of collagenase expression, such as the endogenous gene product itself, steroid hormones and/or the products of cell-cell interactions. These studies will be correlated with those employing cell-free translation of collagenase to determine the nature of the primary collagenase gene product(s) and to determine if modulations in collagenase expression in intact cells are reflected by changes in translatable mRNA. These investigations of normal biosynthetic regulation will be used as a basis for defining the nature of the defect resulting in enhanced synthesis of an aberrant form of collagenase in recessive dystrophic epidermolysis bullosa. Here, both biosynthetic and preparative methods will be used to characterize the regulatory defect and the putatively mutant procollagenase(s) and to establish the therapeutic potential of certain pharmacologic agents. In addition, we shall examine the genetic specificty of any aberration in synthesis and/or structure of collagenase. The biologic importance of these studies is not only to define the normal regulatory mechanisms for collagen degradation but also to develop accurate in vitro markers and rational therapeutic modalities for a devasting genetic cutaneous disease.