M2c型巨噬细胞介导成纤维细胞向肌成纤维细胞转化促进增生性瘢痕形成的作用及机制研究

M2型巨噬细胞与增生性瘢痕形成关系密切，但M2c型巨噬细胞的功能却不甚明确。文献回顾发现，巨噬细胞极化调节因子c-MAF可转录调节IL-10表达，促进M2c型巨噬细胞形成；课题组研究发现，增生性瘢痕中c-MAF阳性的M2型巨噬细胞与肌成纤维细胞数量成正相关；体外实验发现M2c型巨噬细胞可分泌TGF-β1，诱导成纤维细胞向肌成纤维细胞转化。综上课题组假设：c-MAF通过上调IL-10表达，促进了M2c型巨噬细胞形成和TGF-β1分泌，导致成纤维细胞向肌成纤维细胞转化和增生性瘢痕形成。为验证上述假设，课题组拟使用增生性瘢痕临床标本，明确M2c型巨噬细胞分布特点及与肌成纤维细胞的关系；构建共培养模型，探明M2c型巨噬细胞对肌成纤维细胞形成的作用及机制；利用c-Maf巨噬细胞特异性敲除小鼠，探索M2c型巨噬细胞在增生性瘢痕形成中的作用。课题的完成有望为增生性瘢痕防治提供新的理论依据和适宜干预靶点。

M2 macrophages are closely related to the formation of hypertrophic scar, but the function of M2c macrophages in hypertrophic scar formation is unclear. Literature review showed that macrophage polarization regulator c-MAF can transcriptionally regulate the expression of IL-10 and promote M2c macrophage polarization; our group found that the number of c-MAF positive M2 macrophages and myofibroblasts had a significantly positive correlation in hypertrophic scars; In vitro study showed that M2c macrophage can secrete TGF-β1, thus leading to fibroblast to myofibroblast transition. To sum up, we proposed that the up-regulation of IL-10 by c-MAF could cause M2c macrophage polarization and TGF-β1 secretion, resulting in fibroblast to myofibroblast transition and hypertrophic scar formation. In order to verify the above assumptions, we intend to use hypertrophic scar specimens to clarify the distribution characteristics of M2c macrophages and the relationship between M2c macrophages and myofibroblasts; we also intend to explore the effects and mechanisms of M2c macrophages on myofibroblast formation using M2c macrophage and fibroblast co-culture system; we intend to explore the role of M2c macrophages in hypertrophic scar formation using c-Maf macrophage specific knockout mice as well. The completion of this project is expected to provide a new theoretical basis and suitable intervention targets for the prevention and treatment of hypertrophic scars.