COLLAGEN BIOSYNTHESIS IN SKIN FIBROBLASTS

胶原蛋白是结缔组织的主要成分。其合成 在许多疾病过程中改变，在纤维化状况中增加， 异常瘢痕形成和受损伤口愈合减少。拟议 研究的目的是了解负责的分子机制 用于：（1）通过苯甲酰肼抑制胶原合成;和（2） 米诺地尔抑制赖氨酰羟化酶表达。中 将要研究的参数是类型特异性胶原蛋白合成， 前胶原mRNA稳定性、前胶原基因转录和 翻译后修饰酶脯氨酰羟化酶和赖氨酰 羟化酶转录机制将用嵌合的 含有胶原或赖氨酰羟化酶启动子序列的基因 与合适的报告基因相连的基因。这些基因将被插入 以检查对启动子活性的影响。最终 这项研究的目的是确定调节分子，并确定 它们与基因相互作用的性质使我们能够设计 可以调节基因表达的其他效应分子。一个 了解米诺地尔或苯甲酸的转录作用 酰肼可能会导致有效的策略，控制过度 纤维化条件下的胶原积累。

Collagen is a major component of connective tissue. Its synthesis is altered in many disease processes, increasing in fibrotic conditions and abnormal scarring and decreasing in impaired wound healing. The proposed studies are aimed at understanding the molecular mechanisms responsible for: (1) Inhibition of collagen synthesis by benzoic hydrazide; and (2) inhibition of lysyl hydroxylase expression by minoxidil. Among the parameters that will be studied are type-specific collagen synthesis, procollagen mRNA stability, procollagen gene transcription and posttranslational modifying enzymes prolyl hydroxylase and lysyl hydroxylase. Transcriptional mechanisms will be explored with chimeric genes containing promoter sequences for collagen or lysyl hydroxylase genes linked to appropriate reporter genes. These genes will be inserted into fibroblasts to examine influences on promoter activity. The eventual goal of this research is to identify regulatory molecules and to define the nature of their interaction with genes enabling us to design additional effector molecules that can modulate gene expression. An understanding of the transcriptional effects of minoxidil or benzoic hydrazide may lead to effective strategies for controlling excessive collagen accumulation in fibrotic conditions.