Parfejevs Vadims, Debbache Julien, Shakhova Olga, Schaefer Simon M, Glausch Mareen, Wegner Michael, Suter Ueli, Riekstina Una, Werner Sabine, Sommer Lukas
Institute of Anatomy, University of Zürich, 8057, Zürich, Switzerland.
Faculty of Medicine, University of Latvia, Raina Blvd., LV 1586, Riga, Latvia.
Nat Commun. 2018 Jan 16;9(1):236. doi: 10.1038/s41467-017-01488-2.
Cutaneous wound healing is a complex process that aims to re-establish the original structure of the skin and its functions. Among other disorders, peripheral neuropathies are known to severely impair wound healing capabilities of the skin, revealing the importance of skin innervation for proper repair. Here, we report that peripheral glia are crucially involved in this process. Using a mouse model of wound healing, combined with in vivo fate mapping, we show that injury activates peripheral glia by promoting de-differentiation, cell-cycle re-entry and dissemination of the cells into the wound bed. Moreover, injury-activated glia upregulate the expression of many secreted factors previously associated with wound healing and promote myofibroblast differentiation by paracrine modulation of TGF-β signalling. Accordingly, depletion of these cells impairs epithelial proliferation and wound closure through contraction, while their expansion promotes myofibroblast formation. Thus, injury-activated glia and/or their secretome might have therapeutic potential in human wound healing disorders.
皮肤伤口愈合是一个复杂的过程,旨在重建皮肤的原始结构及其功能。在其他疾病中,已知周围神经病变会严重损害皮肤的伤口愈合能力,这揭示了皮肤神经支配对于正常修复的重要性。在此,我们报告周围神经胶质细胞在这一过程中起着关键作用。利用伤口愈合的小鼠模型,结合体内命运图谱,我们发现损伤通过促进去分化、细胞周期重新进入以及细胞向伤口床的扩散来激活周围神经胶质细胞。此外,损伤激活的神经胶质细胞上调许多先前与伤口愈合相关的分泌因子的表达,并通过旁分泌调节转化生长因子-β信号促进肌成纤维细胞分化。因此,这些细胞的缺失会损害上皮细胞增殖和通过收缩实现的伤口闭合,而它们的扩增则促进肌成纤维细胞形成。因此,损伤激活的神经胶质细胞和/或它们的分泌组在人类伤口愈合障碍中可能具有治疗潜力。