Angiogenic properties of myofibroblasts isolated from normal human skin wounds
| Autor: | Dominique Mayrand, Sébastien Larochelle, Audrey Laforce-Lavoie, Véronique J. Moulin, Hervé Genest, Amélie Langlois, Michel Roy |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Collagen Type IV Male Cancer Research Pathology medicine.medical_specialty Physiology Angiogenesis Clinical Biochemistry Basic fibroblast growth factor Neovascularization Physiologic Cell Separation Extracellular matrix Neovascularization chemistry.chemical_compound medicine Humans Fibroblast Myofibroblasts Tissue Inhibitor of Metalloproteinase-3 Wound Healing Tissue Inhibitor of Metalloproteinase-1 integumentary system Chemistry Granulation tissue Dermis Extracellular Matrix Vascular endothelial growth factor medicine.anatomical_structure Cancer research Wounds and Injuries Female sense organs medicine.symptom Wound healing |
| Zdroj: | Angiogenesis. 15(2) |
| ISSN: | 1573-7209 |
| Popis: | During wound healing, angiogenesis plays a crucial role in inducing adequate perfusion of the new tissue, thereby allowing its survival. This angiogenic process contributes to the formation of granulation tissue, alongside myofibroblasts. Myofibroblasts are cells specialized in wound contraction and synthesis of new extracellular matrix. Fibroblasts, considered by some to be at the origin of myofibroblasts, have already been shown to promote neovascularization. Thus, we hypothesized that myofibroblasts play a key role during angiogenic development in wound healing. We isolated myofibroblasts from normal human skin wounds and dermal microvascular endothelial cells (HDMVEC) and fibroblasts from skin. Using an in vitro fibrin-based model, we compared the proangiogenic activity of wound myofibroblasts to that of fibroblasts in the presence of HDMVEC. By immunostaining with collagen IV antibodies, we observed the formation of a capillary network significantly more developed when HDMVEC were cultured with myofibroblasts compared to the network formed in the presence of fibroblasts. The differences between these cell types did not result from a differential secretion of Vascular Endothelial Growth Factor or basic Fibroblast Growth Factor. However, in the presence of myofibroblasts, a significant decrease in matrix metalloproteinase activity was observed. This finding was correlated with a significant increase in Tissue Inhibitor of MetalloProteinase (TIMP)-1 and TIMP-3. Furthermore, inhibition of TIMP-1 secretion using shRNA significantly decreased myofibroblasts induced angiogenesis. These results led to the hypothesis that normal wound myofibroblasts contribute to the vascular network development during wound healing. Our data emphasize the critical role of wound myofibroblasts during healing. |
| Databáze: | OpenAIRE |
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