Qi, Jian Hua and Dai, Ganying and Luthert, Philip and Chaurasia, Shyam and Hollyfield, Joe and Weber, Bernhard H. F. and Stoehr, Heidi and Anand-Apte, Bela (2009) S156C Mutation in Tissue Inhibitor of Metalloproteinases-3 Induces Increased Angiogenesis. JOURNAL OF BIOLOGICAL CHEMISTRY, 284 (30). pp. 19927-19936. ISSN 0021-9258, 1083-351X
Full text not available from this repository. (Request a copy)Abstract
Tissue Inhibitor of metalloproteinases-3 (TIMP-3) is a potent matrix-bound angiogenesis inhibitor. Mutations in TIMP-3 cause Sorsby Fundus Dystrophy, a dominant inherited, early onset macular degenerative disease, with choroidal neovascularization causing a loss of vision in the majority of patients. Here we report that expression of S156C TIMP-3 mutation in endothelial cells results in an abnormal localization of the protein, increased glycosylation, decreased matrix metalloproteinase inhibitory activity, and increased vascular endothelial growth factor (VEGF) binding with a consequent increase in VEGF-dependent migration and tube formation. These enhanced signaling events appear to be mediated as a consequence of a post-transcriptionally regulated increase in the expression of membrane-associated VEGFR-2 in endothelial cells of Timp-3(156/156) mutant mice as well as in human Sorsby fundus dystrophy eyes. Understanding the mechanism(s) by which mutant TIMP-3 can induce abnormal neovascularization provides important insight into the pathophysiology of a number of diseases with increased angiogenesis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SORSBYS-FUNDUS-DYSTROPHY; UNUSUAL CLINICAL-FEATURES; PIGMENT EPITHELIAL-CELLS; CHOROIDAL NEOVASCULARIZATION; VEGF RECEPTOR-2; BRUCHS MEMBRANE; TIMP3; APOPTOSIS; DEATH; LOCALIZATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Sep 2020 09:19 |
| Last Modified: | 10 Sep 2020 09:19 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28696 |
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