Genetic Analysis of Connective Tissue Growth Factor as an Effector of Transforming Growth Factor β Signaling and Cardiac Remodeling
| Autor: | Joseph E. Rabinowitz, Federica Accornero, Allen J. York, John W. Elrod, Michelle A. Sargent, Jop H. van Berlo, Robert N. Correll, Jeffery D. Molkentin, Andrew Leask |
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| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Cardiac fibrosis medicine.medical_treatment Gene Expression Connective tissue Mice Transgenic Mice Transforming Growth Factor beta Fibrosis Internal medicine medicine Animals Molecular Biology Cells Cultured Pressure overload integumentary system biology Myocardium Growth factor Connective Tissue Growth Factor Articles Cell Biology Transforming growth factor beta medicine.disease Up-Regulation Mice Inbred C57BL CTGF Endocrinology medicine.anatomical_structure Gene Targeting biology.protein Cancer research Gene Deletion Signal Transduction Transforming growth factor |
| Zdroj: | Molecular and Cellular Biology. 35:2154-2164 |
| ISSN: | 1098-5549 |
| Popis: | The matricellular secreted protein connective tissue growth factor (CTGF) is upregulated in response to cardiac injury or with transforming growth factor β (TGF-β) stimulation, where it has been suggested to function as a fibrotic effector. Here we generated transgenic mice with inducible heart-specific CTGF overexpression, mice with heart-specific expression of an activated TGF-β mutant protein, mice with heart-specific deletion of Ctgf, and mice in which Ctgf was also deleted from fibroblasts in the heart. Remarkably, neither gain nor loss of CTGF in the heart affected cardiac pathology and propensity toward early lethality due to TGF-β overactivation in the heart. Also, neither heart-specific Ctgf deletion nor CTGF overexpression altered cardiac remodeling and function with aging or after multiple acute stress stimuli. Cardiac fibrosis was also unchanged by modulation of CTGF levels in the heart with aging, pressure overload, agonist infusion, or TGF-β overexpression. However, CTGF mildly altered the overall cardiac response to TGF-β when pressure overload stimulation was applied. CTGF has been proposed to function as a critical TGF-β effector in underlying tissue remodeling and fibrosis throughout the body, although our results suggest that CTGF is of minimal importance and is an unlikely therapeutic vantage point for the heart. |
| Databáze: | OpenAIRE |
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