The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.
Mater Research Institute - The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
Front Endocrinol (Lausanne). 2022 Aug 22;13:957833. doi: 10.3389/fendo.2022.957833. eCollection 2022.
Wnt signaling controls blood vessel growth, regression and patterning during embryonic and postnatal life. Macrophages are major producers of Wnt ligands and angiogenic growth factors. It regulates vascular development and specification during embryogenesis and wound healing. Macrophage dysregulation in wound healing impairs vessel regeneration and delay wound closure. During cutaneous wound healing, the endovascular progenitors (EVPs) proliferate and differentiate into mature endothelial (D) cells in response to signals produced by perivascular cells, including macrophages, governing blood vessels regeneration. However, the role of macrophage's Wnt production on endothelial cells, especially the EVPs during wound healing is currently unknown. Here we used a cutaneous excisional wound model in mice with conditional deletion of Wnt secretion by myeloid cells ( ) to assess the kinetics of endothelial subpopulations (including EVP), myeloid infiltration, collagen deposition and wound closure. Deletion of expression by myeloid cells did not affect wound closure and collagen deposition, indicating that myeloid expression does not promote wound healing and regeneration. Myeloid-specific deletion elevated the EVP population during the peak of angiogenesis, yet without affecting blood vessel density. Wounds in animals showed unperturbed myeloid infiltration and differentiation. Overall, our data indicate that macrophage Wnt production shapes EVP kinetics without major relevance to wound healing. These findings extend the knowledge of macrophage and endothelial molecular crosstalk and position myeloid-derived Wnt production as a regulator of endovascular progenitor.
Wnt 信号在胚胎期和出生后控制血管的生长、退化和模式形成。巨噬细胞是 Wnt 配体和血管生成生长因子的主要产生者。它调节胚胎发生和伤口愈合过程中的血管发育和特化。巨噬细胞在伤口愈合中的失调会损害血管再生并延迟伤口闭合。在皮肤伤口愈合过程中，血管内祖细胞 (EVP) 增殖并分化为成熟的内皮 (D) 细胞，以响应血管周围细胞（包括巨噬细胞）产生的信号，从而控制血管再生。然而，巨噬细胞 Wnt 产生对内皮细胞，特别是在伤口愈合过程中的 EVP 的作用目前尚不清楚。在这里，我们使用条件性缺失骨髓细胞 Wnt 分泌的小鼠皮肤切除伤口模型（）来评估内皮细胞亚群（包括 EVP）、髓系浸润、胶原沉积和伤口闭合的动力学。髓系细胞中 表达的缺失不影响伤口闭合和胶原沉积，表明髓系 表达不会促进伤口愈合和再生。髓系特异性 缺失增加了血管生成高峰期的 EVP 群体，但不影响血管密度。 动物的伤口显示出未受干扰的髓系浸润和分化。总体而言，我们的数据表明，巨噬细胞 Wnt 的产生塑造了 EVP 的动力学，但与伤口愈合没有主要关系。这些发现扩展了对巨噬细胞和内皮细胞分子相互作用的认识，并将骨髓细胞衍生的 Wnt 产生定位为血管内祖细胞的调节剂。
