CONTROL OF COLLAGENASE IN HUMAN FIBROBLAST CULTURES

胶原酶是能够降解天然胶原的酶， 在调节正常人和正常人的胶原蛋白重塑中起重要作用， 病理情况。 对监管机制的理解 胶原酶在体外的表达应该提供了深入了解在体内 这些酶在皮肤疾病中的重要性。 这些研究 并检查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 研究将与那些采用无细胞翻译的研究相关， 胶原酶，以确定初级胶原酶基因的性质 并确定是否调节胶原酶表达， 完整的细胞通过可翻译mRNA的变化来反映。 这些 对正常生物合成调节的研究将作为基础， 用于限定缺陷的性质，导致增强的 隐性营养不良性表皮病中胶原酶的异常形式 大疱 在这里，生物合成和制备方法都将用于 表征调节缺陷和pupirate突变体 前胶原酶，并建立某些 药物制剂。 此外，我们还将检查遗传特异性 胶原酶的合成和/或结构中的任何畸变。 的 这些研究的生物学意义不仅在于确定正常的 胶原蛋白降解的调节机制，而且还可以开发准确的 体外标记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.