Possible roles of TIMP-3 in the morphogenesis of vascular endothelial cells

• Main Authors: Chunyi Chen, 陳君怡
• Other Authors: Jankan Chen
• Format: Others
• Language: en_US
• Published: 2001
• Online Access: http://ndltd.ncl.edu.tw/handle/68428424555665789545

碩士 === 長庚大學 === 基礎醫學研究所 === 89 === Angiogenesis is essential for normal development and is implicated in many pathological processes. The initial step of angiogenesis is proteolysis of the underlying basement menbrane and stroma. The balance between the metalloproteinases and their inhibitors is important in neovascularization and the regulation of extracellular matrix remodeling. In this study, we transfect endothelial cells with TIMP-3 gene using adenovirus-mediated gene transfer system and examine its effect on the fibroblast-induced morphogenesis of human umbilical vein endothelial cell (HUVEC). Infection of HUVEC with recombinant replication-deficient adenoviruses coding for TIMP-3 resulted in marked secretion and accumulation of the TIMP-3 protein to the cell matrix. Overexpression of TIMP-3 inhibited endothelial cell migration in a transfection titer-dependent manner. In addition, overproduction of TIMP-3 reduced the capillary like tube formation, when cocultured with human limbal fibroblasts in three-dimensional collagen gels. These results suggest that connective tissue fibroblast is a source of angiogenic signal and TIMP-3 protein play a crucial role in angiogenesis.