Skin & Endothelium Research Division (SERD), Department of Dermatology, Medical University of Vienna, Anna Spiegel Center of Translational Research, Vienna, Austria.
Skin & Endothelium Research Division (SERD), Department of Dermatology, Medical University of Vienna, Anna Spiegel Center of Translational Research, Vienna, Austria.
J Invest Dermatol. 2022 Jun;142(6):1737-1748.e5. doi: 10.1016/j.jid.2021.11.026. Epub 2021 Dec 16.
Patients suffering from large scars such as burn victims not only encounter aesthetic challenges but also ongoing itching or pain that substantially deteriorates their quality of life. Skin appendages such as hair follicles rarely regenerate within the healing wound. Because they are crucial for skin homeostasis and the lack thereof constitutes one of the main limitations to scarless wound healing, their regeneration represents a major objective for regenerative medicine. Fibroblasts, the main resident cell type of the skin dermis, mediate embryonic hair follicle morphogenesis and are particularly involved in wound healing because they orchestrate extracellular matrix remodeling and collagen deposition in the wound bed. Importantly, dermal fibroblasts originate from two distinct developmental lineages with unique functions that differently mediate the response to epidermal signals such as Hedgehog signaling. In this study, we show that Hedgehog signaling in the reticular fibroblast lineage promotes the initial phase of wound repair, possibly by modulating angiogenesis and fibroblast proliferation, whereas Hedgehog signaling in papillary fibroblasts is essential to induce de novo hair follicle formation within the healing wound.
患有大面积疤痕的患者，如烧伤患者，不仅面临着美观方面的挑战，还伴随着持续的瘙痒或疼痛，这极大地降低了他们的生活质量。皮肤附属物，如毛囊，在愈合的伤口中很少再生。由于它们对皮肤稳态至关重要，而缺乏这些附属物是无瘢痕愈合的主要限制因素之一，因此它们的再生代表了再生医学的主要目标。成纤维细胞是皮肤真皮的主要常驻细胞类型，介导胚胎毛囊形态发生，并且特别参与伤口愈合，因为它们协调细胞外基质重塑和胶原蛋白在伤口床上的沉积。重要的是，真皮成纤维细胞来源于具有独特功能的两个不同发育谱系，它们以不同的方式介导对表皮信号（如 Hedgehog 信号）的反应。在这项研究中，我们表明，网状成纤维细胞谱系中的 Hedgehog 信号促进了伤口修复的初始阶段，可能通过调节血管生成和成纤维细胞增殖来实现，而在乳头状成纤维细胞中的 Hedgehog 信号对于诱导愈合伤口内的新毛囊形成是必不可少的。
