Department of Biological Sciences, Kent State University, Kent, Ohio, USA.
School of Biomedical Sciences, Kent State University, Kent, Ohio, USA.
J Invest Dermatol. 2018 Jan;138(1):219-227. doi: 10.1016/j.jid.2017.08.034. Epub 2017 Sep 9.
The process of wound repair requires the coordinated participation of multiple types of cells, which are sequentially recruited during the healing process. In response to tissue injury, both macrophages and mesenchymal stem cells (MSCs) are recruited to the site of injury, where they participate in the repair process. Despite considerable understanding of the role of each cell type in the process of wound repair, the nature of the dynamic interplay between these two cell types and how this interaction influences the process of wound repair are not well understood. Here, using an in vivo model of cutaneous wound healing in mice, we provide evidence that GPNMB is functionally important in promoting the recruitment of MSCs to the site of skin injury, which in turn modulates inflammatory responses by directing the M2 polarization of macrophages in acute wound healing. Furthermore, we show that GPNMB activity is impaired in a diabetic wound environment, which is associated with impaired MSC recruitment that is reversed by the topical administration of recombinant GPNMB protein to the wounds of diabetic mice. Our study provides important insight into the crosstalk between macrophages and endogenous MSCs toward wound repair.
伤口修复过程需要多种类型的细胞协调参与，这些细胞在愈合过程中依次募集。在组织损伤时，巨噬细胞和间充质干细胞（MSCs）都被募集到损伤部位，参与修复过程。尽管人们对每种细胞类型在伤口修复过程中的作用有了相当的了解，但这两种细胞类型之间动态相互作用的性质以及这种相互作用如何影响伤口修复过程尚不清楚。在这里，我们使用小鼠皮肤伤口愈合的体内模型，提供了证据表明 GPNMB 在促进 MSCs 募集到皮肤损伤部位方面具有重要的功能作用，这反过来又通过指导巨噬细胞的 M2 极化来调节急性伤口愈合中的炎症反应。此外，我们还表明，在糖尿病伤口环境中，GPNMB 活性受损，这与 MSCs 募集受损有关，而向糖尿病小鼠伤口局部给予重组 GPNMB 蛋白可逆转这种募集受损。我们的研究为巨噬细胞和内源性 MSCs 之间在伤口修复方面的相互作用提供了重要的见解。
