增生性瘢痕是继发于烧创伤及术后的常见病，是修复重建外科临床亟待解决的难题。炎症是瘢痕与纤维化的重要因素，但机制尚不明确。近期研究表明，M2型巨噬细胞通过细胞募集，分泌细胞因子与调控代谢等层面参与了病理纤维化的发展，说明该细胞是其潜在的治疗靶点。而巨噬细胞集落刺激因子M-CSF及其受体c-Fms介导了巨噬细胞趋化、增殖、M2型极化，该信号通路在脏器纤维化疾病中激活，提示其调控M2型巨噬细胞参与纤维化的关键作用。而项目组前期研究证实瘢痕内M2型巨噬细胞，M-CSF表达与瘢痕Vancouver评分呈正相关。因此，本项目提出“通过阻断M-CSF/c-Fms通路，抑制M2型巨噬细胞，治疗增生性瘢痕”假说。拟应用重组蛋白及药物抑制剂靶向干预M-CSF/c-Fms，研究对瘢痕增生与免疫调控作用；探讨巨噬细胞诱导成纤维细胞增殖、胶原新生与纤维化通路激活的作用，为靶向免疫调节治疗增生性瘢痕提供理论基础。

Hypertrophic scars form as a result of aberrations of physiologic wound healing and commonly develop following burn injury, lacerations, and surgery. The immune response is a well-known Key factor for scar formation. However, the fundamental mechanism remains unknown. As a result, the current treatment strategy is still based the anti-inflammatory effects of the corticosteroids. Latest researches showed that M2 macrophages are important regulators of pathologic fibrosis and the M-CSF/c-fms signaling was the main regulatory pathways for chemotaxis, proliferation and polarization of the macrophages. The M-CSF/c-fms signaling is also involved in the cirrhosis, pulmonary fibrosis and other fibrotic diseases. Our previous study showed that the M2 macrophages, the M-CSF were significantly correlated with the Vancouver scoring. As a result, we prepare to study the involvement of the M-CSF/c-fms signaling with a scarring mouse model and macrophage-fibroblast co-culture system. The recombinant M-CSF and selective c-FMS inhibitor GW2580 will be used as activation and blockage, respectively. The fibrogenic role and immunomodulatory effects will be studied. Through our research, we aim to explore the role of M-CSF/c-fms signaling in scar formation in order to create a targeted immunomodulatory approach for the treatment of hypertrophic scars.