COLLAGEN BIOSYNTHESIS IN CONNECTIVE TISSUE DISEASE

胶原蛋白是身体的主要结构蛋白， 包括皮肤、骨、腱、软骨 肺角膜和心脏瓣膜 适当的胶原蛋白生物合成需要 精确编排大量转录和翻译后的 步骤包括调节类型特异性胶原蛋白生物合成， 脯氨酸和赖氨酸羟基化，羟基赖氨酸的糖基化， 二硫键形成，转运至细胞外空间，酶促 延伸肽的切除、原纤维形成和交联。 在这种连续的生物合成方案中的扰动可能会被预期为 导致结缔组织结构改变和疾病。 个人 已经在患者中描述了胶原蛋白生物合成的异常 临床上表现为埃勒斯-当洛斯综合征，成骨不全， 皮肤拉克萨 我们建议研究皮肤中胶原蛋白的生物合成 从这些研究胶原生物合成的患者中获得的成纤维细胞 在从这些和其他遗传性疾病患者中获得的皮肤成纤维细胞中， 结缔组织疾病。 胶原蛋白的以下参数 将测量生物合成：（1）类型特异性胶原蛋白合成，（2） 前胶原的合成和前胶原的加工，（3）前胶原的合成， 糖基化羟赖氨酸，（4）可还原交联的合成，（5） 赖氨酰羟化酶脯氨酰羟化酶和赖氨酰的水平，（6） 胶原特异性mRNA;（7）胶原基因的结构。 希望 这些研究将使我们更好地了解这些疾病， 生化水平。 这样的理解是理性的前提 产前诊断、遗传咨询和治疗管理。

Collagen is the major structural protein of the body and as such provides the framework for all tissues including skin, bone, tendon, cartilage, lung, cornea, and heart valve. Proper collagen biosynthesis requires a precise orchestration of a number of transcriptional and post-translation steps including regulation of type-specific collagen biosynthesis, hydroxylation of proline and lysine, glycosylation of hydroxylysine, disulfide bond formation, transport to the extracellular space, enzymatic excision of extension peptides, fibril formation, and cross-linking. Perturbation in this sequential biosynthetic scheme might be expected to result in structurally altered connective tissue and disease. Individual abnormalities in collagen biosynthesis have been described in patients presenting clinically with Ehlers-Danlos syndrome, osteogenesis imperfecta, and cutis laxa. We propose to study collagen biosynthesis in skin fibroblasts obtained from patients with these study collagen biosynthesis in skin fibroblasts obtained from patients with these and other inherited disorders of connective tissue. The following parameters of collagen biosynthesis will be measured: (1) type-specific collagen synthesis, (2) synthesis of procollagen and processing of procollagen, (3) synthesis of glycosylated hybroxylysine, (4) synthesis of reducible cross-links, (5) levels of lysyl hydroxylase prolyl hydroxylase and lysyl, (6) levels of collagen specific mRNA, and (7) structure of collagen genes. It is hoped that these studies will allow us to better understand these diseases at a biochemical level. Such understanding is a prerequisite for rational prenatal diagnosis, genetic counseling, and therapeutic management.