The nucleic acid scavenger polyamidoamine third-generation dendrimer inhibits fibroblast activation and granulation tissue contraction
| Autor: | Tosan Ehanire, Maria Angelica Selim, Howard Levinson, Jennifer E. Bond, Eda K. Holl, Bruce A. Sullenger |
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| Rok vydání: | 2014 |
| Předmět: |
Pathology
medicine.medical_specialty Dendrimers Contraction (grammar) Cellular differentiation Real-Time Polymerase Chain Reaction Article Cicatrix Mice Cell Movement Nucleic Acids Polyamines Medicine Animals Humans Fibroblast health care economics and organizations Cells Cultured Wound Healing business.industry Toll-Like Receptors Granulation tissue Cell Differentiation Fibroblasts Immunohistochemistry Cell biology Mice Inbred C57BL Real-time polymerase chain reaction medicine.anatomical_structure Microscopy Fluorescence Nucleic acid Granulation Tissue Cytokines Surgery Signal transduction business Wound healing Biomarkers Signal Transduction |
| Zdroj: | Plastic and reconstructive surgery. 134(3) |
| ISSN: | 1529-4242 |
| Popis: | Pathologic cutaneous scarring affects over 40 million people worldwide and costs billions of dollars annually. Understanding mechanisms of fibroblast activation and granulation tissue contraction is the first step toward preventing pathologic scarring. The authors hypothesize that nucleic acids increase fibroblast activation and cause granulation tissue contraction and that sequestration of nucleic acids by application of a nucleic acid scavenger dendrimer, polyamidoamine third-generation dendrimer, will decrease pathologic scarring.In vitro experiments were performed to assess the effect of nucleic acids on pathologic scar-associated fibroblast activity. The effect of nucleic acids on cytokine production and migration on mouse fibroblasts was evaluated. Immunofluorescence microscopy was used to determine the effect of nucleic acids on the differentiation of human primary fibroblasts into myofibroblasts. Using a murine model, the effect of polyamidoamine third-generation dendrimer on granulation tissue contraction was evaluated by gross and histologic parameters.Mouse fibroblasts stimulated with nucleic acids had increased cytokine production (i.e., transforming growth factor-β, monocyte chemotactic protein 1, interleukin-10, tumor necrosis factor-α, and interferon-γ), migration, and differentiation into myofibroblasts. Polyamidoamine third-generation dendrimer blocked cytokine production, migration, and differentiation into myofibroblasts. Using a murine model of granulation tissue contraction, polyamidoamine third-generation dendrimer decreased wound contraction and angiogenesis. Collagen deposition in polyamidoamine third-generation dendrimer-treated tissues was aligned more randomly and whorl-like compared with control tissue.The data demonstrate that nucleic acid-stimulated fibroblast activation and granulation tissue contraction are blocked by polyamidoamine third-generation dendrimer. Sequestration of pathogen-associated molecular patterns may be an approach for preventing pathologic scarring. |
| Databáze: | OpenAIRE |
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