Jararhagin-C, a disintegrin-like protein, improves wound healing in mice through stimulation of M2-like macrophage, angiogenesis and collagen deposition
Autor: | Tatiana Carla Tomiosso, Lucíola S. Barcelos, Patricia Bianca Clissa, Bruno Antonio Ferreira, Luiz Ricardo Goulart, Francyelle Borges Rosa de Moura, Natássia Caroline Resende Corrêa, Fernanda de Assis Araújo |
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Rok vydání: | 2021 |
Předmět: |
Angiogenesis
Cell Survival medicine.medical_treatment Disintegrins Immunology Macrophage polarization Neovascularization Physiologic Inflammation Pharmacology Fibroblast growth factor Mice Crotalid Venoms medicine Human Umbilical Vein Endothelial Cells Leukocytes Immunology and Allergy Macrophage Animals Humans RNA Messenger Wound Healing Chemistry Macrophages CXCL1 Cytokine Gene Expression Regulation Cytokines Collagen medicine.symptom Wound healing |
Zdroj: | International immunopharmacology. 101 |
ISSN: | 1878-1705 |
Popis: | Jararhagin-C (Jar-C) is a disintegrin-like protein, isolated from the venom of B. jararaca, with affinity for α2β1 integrin and the ability to incite processes such as angiogenesis and collagen deposition in vivo. Thus, we raised the hypothesis that this protein could be used as a therapeutic strategy for stimulating the healing of excisional wounds in mice. Four wounds were made on the back of Swiss mice, treated with daily intradermal injections of PBS (control group) or Jar-C (200 ng). Ten animals from each experimental group were euthanized and the tissue from the wounds and skin around them were collected for further biochemical, histological and molecular analysis. Wounds treated with Jar-C showed a faster closure rate, accompanied by a reduction in neutrophil infiltrate (MPO), pro-inflammatory cytokine levels (TNF, CXCL1 and CCL2) and an accumulation of macrophages in the analyzed tissues. It was also observed a greater expression of genes associated with the phenotype of alternatively activated macrophages (M2). Concomitantly, the administration of Jar-C holds an angiogenic potential, increasing the density of blood vessels and the synthesis of pro-angiogenic cytokines (VEGF and FGF). We also observed an increase in collagen deposition, accompanied by higher levels of the pro-fibrogenic cytokine TGF-β1. Our data suggests Jar-C stimulates wound healing through stimulation of M2-like macrophage, angiogenesis and collagen deposition. Jar-C may be explored as a therapeutic strategy for wound healing, including the treatment of chronic wounds, where processes such as inflammation, angiogenesis and the deposition / remodeling of the matrix constituents are unregulated. |
Databáze: | OpenAIRE |
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