Differential and combined effects of cardiotrophin-1 and TGF-beta1 on cardiac myofibroblast proliferation and contraction
| Autor: | Sunil G. Rattan, Ryan H. Cunnington, Ian M.C. Dixon, Kristen M. Bedosky, Vanja Drobic, Vinit V. Elimban, Joshua E. Raizman |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
DNA Replication
Male Contraction (grammar) Time Factors Cardiotrophin 1 Physiology Becaplermin Myocardial Infarction Biology Transfection Collagen Type I Smad7 Protein Rats Sprague-Dawley Transforming Growth Factor beta1 Physiology (medical) Cyclin E medicine Myocyte Animals Drug Interactions Myocytes Cardiac Myocardial infarction Cells Cultured Cell Proliferation Platelet-Derived Growth Factor Wound Healing Dose-Response Relationship Drug Myocardium Cyclin-Dependent Kinase 2 Proto-Oncogene Proteins c-sis Fibroblasts medicine.disease Myocardial Contraction Rats Phenotype Immunology Circulatory system Cancer research Cytokines Cardiology and Cardiovascular Medicine Wound healing Myofibroblast Gels Cyclin-Dependent Kinase Inhibitor p27 Transforming growth factor |
| Zdroj: | American journal of physiology. Heart and circulatory physiology. 293(2) |
| ISSN: | 0363-6135 |
| Popis: | Myofibroblasts respond to an array of signals from mitogens and cytokines during the course of wound healing following a myocardial infarction (MI), and these signals may coordinate ventricular myofibroblast proliferation. Furthermore, myofibroblasts are contractile and contribute to wound contraction by imparting mechanical tension on surrounding extracellular matrix. Although TGF-β1, CT-1, and PDGF-BB participate in various stages of post-MI wound healing, their combined net effect(s) on myofibroblast function is unknown. We investigated myofibroblast proliferation, expression of cell cycle proteins, and contractile function of cells treated with TGF-β1and/or CT-1. We confirmed that TGF-β1(10 ng/ml) suppresses proliferation of these cells, whereas CT-1 (10 ng/ml) and, for comparative purposes, PDGF-BB (1 ng/ml) treatments were associated with proliferation. Specific TGF-β1treatment ablated CT-1-induced myofibroblast proliferation. TGF-β1effects were specific, as they were suppressed by either TGF-β-neutralizing antibody or viral Smad7 overexpression. TGF-β1treatment also increased expression of p27 and decreased expression of cyclin E and Cdk2 in primary cells. CT-1 (10 ng/ml) treatment of myofibroblasts had no effect on collagen gel deformation versus controls, whereas TGF-β1(10 ng/ml) and PDGF (10 ng/ml) treatments were associated with significant cell contraction; again, TGF-β1-mediated contraction was unaffected by CT-1. Alone, CT-1 and TGF-β1treatments exert opposing effects on myofibroblast function, whereas in combination TGF-β1-mediated effects supersede those of CT-1 (and PDGF-BB). Thus TGF-β1and CT-1 exert differential effects on myofibroblast proliferation and contraction in vitro, and we suggest that a balance of these effects may be important for the execution of normal cardiac wound healing. |
| Databáze: | OpenAIRE |
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