BIOLOGY AND MOLECULAR BIOLOGY OF TRANSFORMING GROWTH FACTOR-BETA

该项目的目的是双重的：研究生物学 转化生长因子-β（TGF-β），特别是在 它对细胞功能的影响，并研究分子 TGF-β的生物学，重点是识别可能的 TGF-β家族的其他成员，并评估 保护物种之间的前体和处理 TGF-β肽。 关于TGF-β的生物学， 该肽对间充质细胞的主要作用 起源是控制基质蛋白的合成。 因此， TGF-β的表达可能有助于 以几种疾病过程为特征的过度纤维化。 事实上，已经有可能将TGF-β的水平与肿瘤的发生、发展和预后相关联。 人类眼睛的玻璃体吸出物，严重程度为 纤维变性疾病、增生性玻璃体视网膜病变。 的其他行 研究表明，已知TGF-β 调节细胞增殖和细胞分化可能 在建立发育中的胚层方面很重要 两栖动物胚胎 使用TGF-β的特异性抗体，以及 作为检测和定量肽的测定，表明TGF-β 1和TGF-β 2是一种特异性的肽。 β可能是从外胚层诱导中胚层所必需的。 这些对胚胎学的兴趣也导致了克隆和 三个新的TGF-β相关蛋白基因的测序 鸡和青蛙胚胎的cDNA文库，以及 鉴定控制TGF-β表达的机制， 作为mRNA的选择性剪接， TGF-β 1启动子的调控区。 了解控制TGF-β表达的机制将 不仅对发育过程很重要， 过程也是。

The purpose of the project is twofold: to study the biology of transforming growth factor-beta (TGF-beta), particularly in terms of its effects on cell function, and to investigate the molecular biology of TGF-beta with emphasis on both identifying possible additional members of the TGF-beta family and evaluating the degree of conservation between species of both the precursor and processed TGF-beta peptides. With respect to the biology of TGF-beta, one of the principal effects of the peptide on cells of mesenchymal origin is to control synthesis of matrix proteins. Thus, aberrant expression of TGF-beta might be expected to contribute to the excessive fibrosis characteristic of several disease processes. Indeed, it has been possible to correlate levels of TGF-beta in vitreous-aspirates of human eyes with the degree of severity of a fibrotic disease, proliferative vitreoretinopathy. Other lines of investigation have shown that the known ability of TGF-beta to regulate cellular proliferation and cellular differentiation might be important in the establishment of the-germ layers of developing amphibian embryo. Use of specific antibodies to TGF-beta, as well as assays to detect and quantitate the peptide, suggest that TGF- beta might be essential in induction of mesoderm from ectoderm. These interests in embryology have also resulted in the cloning and sequencing of three new genes for proteins related to TGF-betas in cDNA libraries of chicken and frog embryos, as well as in identification of mechanisms of control of TGF-beta expression such as alternate splicing of mRNAs and specific positive and negative regulatory control regions of the TGF-beta 1 promoter. Understanding the mechanisms which control TGF-beta expression will be important not only to developmental processes, but to disease processes as well.