30%-90%的人曾发生增生性瘢痕和瘢痕疙瘩，治疗方法多样但治疗后复发率高，因此探究瘢痕疙瘩的发病机制显得尤为重要。前期对瘢痕疙瘩组织及细胞进行转录组测序显示S100A9在瘢痕疙瘩中显著升高，但在瘢痕成纤维细胞中反而降低，并可能通过PI3K、TGF-β等通路发挥作用。S100A9蛋白主要由角质形成细胞表达，激活成纤维细胞，促进组织损伤修复及间质纤维化，RAGE抑制剂可削弱这一作用。结合前期研究及文献报道，我们推测，S100A9可能通过活化RAGE信号通路促进瘢痕疙瘩的形成。基于此，本课题设计拟采用重组蛋白、基因转染及细胞条件性重编程、细胞共培养、组织工程学技术、小鼠移植模型模拟瘢痕的形成，研究S100A9对成纤维细胞、角质形成细胞增殖分化、胶原沉积等的影响，及与RAGE以及下游通路间的作用关系。通过研究为优化瘢痕疙瘩动物模型，阐明瘢痕疙瘩新的发病机理以及S100A9作为治疗靶点的可能。

Keloids and hypertrophic scars occur anywhere from 30 to 90% of patients. To date, the patients with keloid and clinical doctors were still puzzled by the high recurrence rate of keloid. So to explore the pathogenesis of keloid is particularly important. Our research about keloid tissue and fibroblasts by high-throughput transcriptome sequencing showed that S100A9 was increased in keloid but decreased in keloid fibroblasts. Signal pathway analysis found that S100A9 may play a role through PI3K, TGF-β. S100A9，mainly expressed in keratinocytes， induced tissue repair and fibrosis by activating fibroblasts，which can be weakened by RAGE inhibitors. However, the role of S100A9 in keloid is still in suspense. According to our study and previous investigations, we hypothesized S100A9 may play a promoting role in keloid by activating RAGE induce downstream signaling. In this study we will use recombinant protein, gene transfect, and conditional reprogramming， human skin three-dimensional culture model, and in vitro keloid scar model and in vivo keloid implantation models to optimize animal model of keloid and investigate that the relationship among S100A9, RAGE and their possible mechanism in keloid formation which possibly supplies new ideas for the pathogenesis and therapeutic strategy of keloid.