Gene expression fingerprinting for human hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) or Osler-Weber-Rendu syndrome is an autosomal dominant vascular disorder characterized by telangiectases and internal arteriovenous malformations. It is caused by mutations in elements of the transforming growth factor-β (TGF-β) receptor complex: endoglin,...

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Bibliographic Details
Published in:Human molecular genetics 2007-07, Vol.16 (13), p.1515-1533
Main Authors: Fernandez-Lopez, Africa, Garrido-Martin, Eva M., Sanz-Rodriguez, Francisco, Pericacho, Miguel, Rodriguez-Barbero, Alicia, Eleno, Nelida, Lopez-Novoa, Jose M., Düwell, Anette, Vega, Miguel A., Bernabeu, Carmelo, Botella, Luisa M.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Adhesion
Cell Movement
Cell Proliferation
Dermatology
Endothelium, Vascular - metabolism
Fundamental and applied biological sciences. Psychology
Gene Expression Profiling
Genetic Predisposition to Disease
Genetics of eukaryotes. Biological and molecular evolution
Hereditary diseases of the skin. Congenital diseases of the skin. Haemangioma of the skin, of mucosae and of soft tissue
Humans
Medical sciences
Mice
Molecular and cellular biology
Neovascularization, Pathologic
Signal Transduction
Telangiectasia, Hereditary Hemorrhagic - genetics
Transforming Growth Factor beta - metabolism
Wound Healing
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Summary:Hereditary hemorrhagic telangiectasia (HHT) or Osler-Weber-Rendu syndrome is an autosomal dominant vascular disorder characterized by telangiectases and internal arteriovenous malformations. It is caused by mutations in elements of the transforming growth factor-β (TGF-β) receptor complex: endoglin, a co-receptor, responsible for HHT1, or ALK1 (activin receptor-like kinase 1), a type I receptor leading to HHT2. Recently, we have established cultures of HHT endothelial cells, primary targets of the disease. These cells showed deficient TGF-β signaling and angiogenesis, representing a useful human model to study the molecular mechanism of this disease. To understand the pathogenic mechanism underlying HHT, we have used total RNA probes to compare HHT versus non-HHT cells by expression microarrays. This work represents a systematic study to identify target genes affected in HHT cells. Given the similarity of symptoms in HHT1 and HHT2, special interest has been put on the identification of common targets for both HHT types. As a result, 277 downregulated and 63 upregulated genes were identified in HHT versus control cells. These genes are involved in biological processes relevant to the HHT pathology, such as angiogenesis, cytoskeleton, cell migration, proliferation and NO synthesis. The type of misregulated genes found in HHT endothelial cells lead us to propose a model of HHT pathogenesis, opening new perspectives to understand this disorder. Moreover, as the disease is originated by mutations in proteins of the TGF-β receptor complex, these results may be useful to find out targets of the TGF-β pathway in endothelium.
ISSN:0964-6906
1460-2083
DOI:10.1093/hmg/ddm069