Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland.
J Invest Dermatol. 2010 Dec;130(12):2818-27. doi: 10.1038/jid.2010.224. Epub 2010 Aug 5.
Ischemic wounds are characterized by oxygen levels lower than that of healthy skin (hypoxia) and poor healing. To better understand the pathophysiology of impaired wound healing, we investigated how switching from high (21%) to low (2%) oxygen levels directly affects cultured skin myofibroblasts, essential cells for the normal wound repair process. Myofibroblast differentiation and function were assessed by quantifying α-smooth muscle actin expression and cell contraction in collagen gels and on wrinkling silicone substrates. Culture for 5 days at 2% oxygen is perceived as hypoxia and significantly reduced myofibroblast differentiation and contraction despite high levels of the profibrotic transforming growth factor-β1. Analysis of α-smooth muscle actin expression on wrinkling substrates over time showed that reduced myofibroblast contraction preceded α-smooth muscle actin disassembly from stress fibers after switching from 21 to 2% oxygen. These effects were reversible by restoring high oxygen conditions and by applying mechanical stress. We suggest that mechanical challenge is a clinical relevant strategy to improve ischemic and chronic wound healing by supporting myofibroblast formation.
缺血性创面的特点是其氧气水平低于健康皮肤（缺氧），且愈合不良。为了更好地理解受损创面愈合的病理生理学，我们研究了从高（21%）氧水平切换到低（2%）氧水平如何直接影响培养的皮肤肌成纤维细胞，这些细胞是正常创面修复过程中的必需细胞。通过定量评估α-平滑肌肌动蛋白的表达和胶原蛋白凝胶中的细胞收缩以及在起皱硅酮基质上的细胞收缩，来评估肌成纤维细胞的分化和功能。在 2%氧气下培养 5 天被视为低氧环境，尽管存在高水平的促纤维化转化生长因子-β1，但仍显著降低了肌成纤维细胞的分化和收缩。随着时间的推移，在起皱的基质上分析α-平滑肌肌动蛋白的表达表明，在从 21%切换到 2%氧气后，肌成纤维细胞收缩减少先于α-平滑肌肌动蛋白从应力纤维上解体。通过恢复高氧条件和施加机械压力，这些影响是可逆的。我们认为，机械挑战是一种临床相关的策略，可以通过支持肌成纤维细胞的形成来改善缺血性和慢性创面愈合。
