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The angiopoietin-like factor cornea-derived transcript 6 is a putative morphogen for human cornea
Ron Peek1, Richard A Kammerer, Sabine Frank
1Department of Molecular Immunology, Netherlands Ophthalmic Research Institute, Amsterdam 1105 BA, The Netherlands. r.peek@ioi.knaw.nl
The Journal of Biological Chemistry
|October 30, 2001
Summary
Cornea-derived transcript 6 (CDT6), a protein in the angiopoietin family, was studied for its role in tissue development. CDT6 expression in a mouse model reduced tumor growth and induced fibrosis, suggesting it acts as a morphogen to promote a corneal phenotype.
Area of Science:
- Biochemistry
- Molecular Biology
- Developmental Biology
Background:
- Cornea-derived transcript 6 (CDT6) is a human cornea-specific protein belonging to the angiopoietin gene family.
- High expression of CDT6 in the avascular corneal stroma suggests a potential role in regulating angiogenesis.
Purpose of the Study:
- To structurally and functionally characterize CDT6.
- To investigate the hypothesis that CDT6 negatively regulates angiogenesis.
- To determine the effect of CDT6 on tissue with high vascular density.
Main Methods:
- Structural and functional characterization of CDT6.
- Expression of CDT6 in a mouse xenograft model to assess its effect on tumor growth and angiogenesis.
- Analysis of extracellular matrix deposition.
Main Results:
- CDT6 is a secreted protein that forms disulfide-linked homotetramers via coiled-coil interactions.
- CDT6 expression in a mouse xenograft model reduced tumor growth and aberrant blood vessel formation.
- CDT6 induced massive fibrosis and deposition of corneal stromal extracellular matrix components.
Conclusions:
- CDT6 functions as a negative regulator of angiogenesis.
- CDT6 acts as a morphogen, inducing a corneal phenotype in vivo through fibrosis and extracellular matrix deposition.