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Biochemical characterization and act...
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Blalock, Timothy Daniel.
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Biochemical characterization and action of connective tissue growth factor and its receptor in corneal scarring.
紀錄類型:
書目-語言資料,印刷品 : Monograph/item
正題名/作者:
Biochemical characterization and action of connective tissue growth factor and its receptor in corneal scarring./
作者:
Blalock, Timothy Daniel.
面頁冊數:
170 p.
附註:
Chair: Gregory S. Schultz.
Contained By:
Dissertation Abstracts International65-01B.
標題:
Biology, Cell. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3120098
ISBN:
9780496674701
Biochemical characterization and action of connective tissue growth factor and its receptor in corneal scarring.
Blalock, Timothy Daniel.
Biochemical characterization and action of connective tissue growth factor and its receptor in corneal scarring.
- 170 p.
Chair: Gregory S. Schultz.
Thesis (Ph.D.)--University of Florida, 2003.
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-beta), 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-beta on contributing to corneal scarring by binding to the type II insulin-like growth factor receptor.
ISBN: 9780496674701Subjects--Topical Terms:
1017686
Biology, Cell.
Biochemical characterization and action of connective tissue growth factor and its receptor in corneal scarring.
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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-beta), 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-beta on contributing to corneal scarring by binding to the type II insulin-like growth factor receptor.
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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-beta. CTGF also mediated the effects of TGF-beta 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-beta-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.
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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.
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