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首页> 外文学位 >Biochemical characterization and action of connective tissue growth factor and its receptor in corneal scarring.
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Biochemical characterization and action of connective tissue growth factor and its receptor in corneal scarring.

机译：结缔组织生长因子及其受体在角膜瘢痕形成中的生化特性和作用。

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摘要

Connective tissue growth factor (CTGF) is a 38 kilodalton, cysteine-rich, secreted peptide with mitotic and chemotactic functions. CTGF expression is upregulated by transforming growth factor beta (TGF-β), leading to the synthesis of connective tissue and extracellular matrix components such as collagen, laminin, integrin, and fibronectin which are predominant components of scar tissue. CTGF mRNA and protein levels are elevated in human fibrotic disorders including renal fibrosis, scleroderma, and keloids. Experimental data suggest that CTGF mediates the effects of TGF-β on contributing to corneal scarring by binding to the type II insulin-like growth factor receptor.; Gene expression profiling experiments, using GeneGhip technology, were performed showing the classes of genes in corneal fibroblasts that are induced upon CTGF stimulation. These results show that CTGF regulates key genes involved in corneal apoptosis, scarring, and angiogenesis. CTGF mRNA and protein expression was stimulated in corneal fibroblasts in response to TGF-β. CTGF also mediated the effects of TGF-β on cell-associated collagen formation. Photorefractive keratectomy (PRK) was performed on rats to show that CTGF mRNA and protein expression increased dramatically in the corneal fibroblasts and epithelial cells after surgery up to Day 21. To reduce corneal fibrosis, a gene-specific hammerhead ribozyme was developed to target and cleave CTGF mRNA to reduce its expression. Cells transfected with a plasmid encoding the CTGF ribozyme showed a marked decrease in CTGF mRNA and protein expression as well as TGF-β-induced cell proliferation. To characterize the receptor for CTGF, radioligand binding, cross-linking, in vitro binding, and immunoprecipitation experiments were performed. These results indicate that CTGF binds to the type II insulin-like growth factor (IGF) receptor in corneal fibroblasts. Binding to this receptor confers biological activity in these cells.; Thus, these experiments show for the first time the induction of CTGF expression in corneal scarring, the application of gene therapy to reduce CTGF expression, and the identity of the CTGF receptor in corneal fibroblasts. Knowledge of the biochemistry and action of CTGF and its receptor will elucidate their roles in the process of wound healing and the development of anti-scarring agents.
机译：结缔组织生长因子（CTGF）是一种38道尔顿，富含半胱氨酸的分泌肽，具有有丝分裂和趋化功能。 CTGF的表达通过转化生长因子β（TGF-β）上调，从而导致结缔组织和细胞外基质成分（如胶原，层粘连蛋白，整联蛋白和纤连蛋白）的合成，这些成分是疤痕组织的主要成分。在包括肾纤维化，硬皮病和瘢痕loid在内的人类纤维化疾病中，CTGF mRNA和蛋白质水平升高。实验数据表明，CTGF通过与II型胰岛素样生长因子受体结合来介导TGF-β促进角膜瘢痕形成。使用GeneGhip技术进行的基因表达谱实验显示了CTGF刺激后诱导的角膜成纤维细胞中的基因类别。这些结果表明，CTGF调节参与角膜凋亡，瘢痕形成和血管生成的关键基因。响应TGF-β，刺激角膜成纤维细胞中CTGF mRNA和蛋白表达。 CTGF还介导TGF-β对细胞相关胶原形成的影响。在大鼠进行光折射性角膜切除术（PRK）后显示，直到手术第21天，CTGF mRNA和蛋白表达在角膜成纤维细胞和上皮细胞中显着增加。为了减少角膜纤维化，开发了一种基因特异性锤头状核酶来靶向和裂解CTGF mRNA减少其表达。用编码CTGF核酶的质粒转染的细胞显示CTGF mRNA和蛋白表达以及TGF-β诱导的细胞增殖明显减少。为了表征CTGF的受体，进行了放射性配体结合，交联，体外结合以及免疫沉淀实验。这些结果表明CTGF与角膜成纤维细胞中的II型胰岛素样生长因子（IGF）受体结合。与该受体的结合赋予这些细胞生物活性。因此，这些实验首次显示了在角膜瘢痕形成中诱导CTGF表达，基因治疗降低CTGF表达的应用以及在角膜成纤维细胞中CTGF受体的身份。 CTGF及其受体的生物化学和作用的知识将阐明它们在伤口愈合和抗瘢痕形成剂开发中的作用。

著录项

  • 作者

    Blalock, Timothy Daniel.;

  • 作者单位

    University of Florida.;

  • 授予单位 University of Florida.;
  • 学科 Health Sciences Ophthalmology.; Biology Molecular.; Chemistry Biochemistry.; Biology Cell.
  • 学位 Ph.D.
  • 年度 2003
  • 页码 p.167
  • 总页数 200
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 R770.1;
  • 关键词

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