PolyI:C促进皮肤伤口愈合中成纤维细胞异质性及细胞间作用机制研究

皮肤伤口愈合障碍目前没有满意治疗手段。研究表明成年动物大于1cm2伤口可诱导含毛囊再生的伤口愈合(WIHN)。损伤释放dsRNA激活TLR3影响IL-6促进伤口愈合，提示损伤信号作用。WIHN的机制是启动骨髓来源的单核细胞转化为成纤维细胞，具体促进伤口愈合的机制不清。我们前期研究证实polyI:C(合成的dsRNA)激活TLR3促进伤口愈合，诱导人真皮成纤维细胞分泌IL-6，巨噬细胞增加，影响成纤维细胞异质性。因此，我们提出polyI:C激活TLR3模拟了大伤口的损伤信号，影响了成纤维细胞的异质性，成纤维细胞分泌IL-6增加，在巨噬细胞的参与下，促进伤口愈合作用的假说。本项目拟在细胞及动物水平上，用单细胞RNA-Seq确定polyI:C影响成纤维细胞异质性，明确polyI:C对IL-6-pSTAT-Gli信号轴及对巨噬细胞的作用，揭示促进伤口愈合分子细胞机制，为伤口愈合提供新的理论认识。

It will be a great burden for the patients with wound heal dysfunction, because there is no specific therapy for abnormal skin wound healing. Recently, some studies found that a large wound (larger than 1cm2 in mice) could promote wound healing with follicle neogenesis. It indicated that the Initiating factors for wound healing being a large wound presenting an injury signal to be recognized, and the cellular mechanism underlying is to recruit myoloid monocyte and transform to fibroblast and myofibroblast. Our previous studies showed that polyI:C accelerated wound healing by activation of TLR3. PolyI:C increased fibroblast released IL-6, and increased the number of macrophages in wound beds. Here, we give rise to a hypothesis that polyI:C as an injury signaling being mimic the large wound injury and effect to affect wound healing via activation of TLR3, fibroblast heterogeneity, IL-6-pSTAT3-Gli axis and activation of macrophage. This study will give a proof for our hypothesis by cell and animal model experiments. We will investigate that polyI:C affect fibroblast heterogeneity, stimulation of interleukin-6, activation of macrophage and human dermal fibroblast proliferation, migration and differentiation. The study will reveal cellular and molecular mechanism of wound healing.