Institute of Biotechnology, Federal University of Uberlândia, UFU, Uberlândia, MG, Brazil; Department of Physiological Sciences, Institute of Biomedical Sciences, Federal University of Uberlândia, UFU, Uberlândia, MG, Brazil.
Department of Cell Biology, Histology and Embryology, Institute of Biomedical Sciences, Federal University of Uberlândia, UFU, Uberlândia, MG, Brazil.
Int Immunopharmacol. 2021 Dec;101(Pt B):108224. doi: 10.1016/j.intimp.2021.108224. Epub 2021 Oct 13.
Jararhagin-C (Jar-C) is a disintegrin-like protein, isolated from the venom of B. jararaca, with affinity for αβ 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.
芋螺毒素-C（Jar-C）是一种从巴西矛头蝮蛇毒液中分离得到的解整合素样蛋白，对αβ整合素有亲和力，并能在体内引发血管生成和胶原沉积等过程。因此，我们提出假设，这种蛋白可以用作刺激小鼠切口愈合的治疗策略。在瑞士小鼠背部制造四个伤口，每天用皮内注射 PBS（对照组）或 Jar-C（200ng）处理。每个实验组有 10 只动物被安乐死，收集伤口和周围皮肤的组织进行进一步的生化、组织学和分子分析。用 Jar-C 处理的伤口愈合速度更快，伴随中性粒细胞浸润（MPO）减少、促炎细胞因子水平（TNF、CXCL1 和 CCL2）降低以及分析组织中巨噬细胞的积累。还观察到与替代激活的巨噬细胞（M2）表型相关的基因表达增加。同时，Jar-C 的给药具有血管生成潜力，增加血管密度和促血管生成细胞因子（VEGF 和 FGF）的合成。我们还观察到胶原沉积增加，伴随促纤维化细胞因子 TGF-β1 水平升高。我们的数据表明，Jar-C 通过刺激 M2 样巨噬细胞、血管生成和胶原沉积来刺激伤口愈合。Jar-C 可能被探索用作伤口愈合的治疗策略，包括治疗慢性伤口，其中炎症、血管生成和基质成分的沉积/重塑等过程不受调节。
