miR-22/PGC-1α/PPAR-γ调控“成纤维细胞-成脂前体样细胞转分化”拮抗烧伤后增生性瘢痕的作用与机制研究

烧伤后增生性瘢痕（HTS）是亟待解决的临床难题。研究表明成纤维细胞过度增殖并转化为肌成纤维细胞（MFB）是其发病的关键，因此阻断该转化途径成为防治HTS的重要策略。我们以此为切入点，发现糖皮质激素可诱导成纤维细胞转分化为成脂前体样细胞。该表型转换抑制了其向MFB转变，并可能引起细胞外基质降解及重构；而预实验提示miR-22/PGC-1α/PPAR-γ通路在促进细胞成脂转分化中起关键调控作用，但分子机制尚不清楚。据此，本课题拟利用细胞、患者HTS组织及动物模型等，研究成脂前体样细胞的新特性及其对细胞外基质的影响，明确成纤维细胞-成脂前体样细胞转分化拮抗HTS的作用；深入探讨miR-22/PGC-1α/PPAR-γ调控成脂转分化的分子机制及干预靶点，并利用通路靶向激活，进一步验证促进细胞成脂转分化抑制HTS的效果。本课题有望阐明调控成纤维细胞成脂转分化拮抗HTS的机制，并为瘢痕防治提供新策略。

Hypertrophic scar (HTS) after burn injury is a serious clinical problem to be solved urgently. Studies have shown that the hyperproliferation of fibroblasts and fibroblast-to-myofibroblast transformation are the key step in the formation of HTS. Thus, blocking the process is expected to prevent scar development. Taking this as a breakthrough point, we found that glucocorticoid can induce the transdifferentiation of fibroblasts to adipogenic precursor-like cells. The phenotypic transformation can inhibit fibroblast-to-myofibroblast transformation and cause the degradation and remodeling of extracellular matrix; In addition, mechanism studies suggested that miR-22/PGC-1α/PPAR-γ pathway may play a key regulatory role in promoting adipogenic transdifferentiation, but the detailed molecular mechanism is unclear. Based on these evidences, the research intends to study the new biological characteristics of adipogenic precursor-like cells and its effect on the extracellular matrix by using cell, HTS tissue and animal model. Thus, to clarify the inhibitory effect of the transdifferentiation of fibroblasts to adipogenic precursor-like cells on HTS. Besides, we hope to further explore the mechanism and intervention targets of miR-22/PGC-1α/PPAR-γ on regulating the transdifferentiation of cells to adipogenic cells, and verify the inhibitory effect of adipogenic transdifferentiation on HTS by targeting activation of the pathway. This study is expected to elucidate the inhibitory effect and mechanism of the transdifferentiation of fibroblasts to adipogenic precursor-like cells on HTS, and to provide a new strategy for scar treatment.