上皮间质转化（EMT）失控导致的增生性瘢痕成纤维细胞（HSF）过度生成是增生性瘢痕（HS）的重要诱因。我们前期证实表皮干细胞（ESCs）能够通过外泌体（Exo）诱导HSF间质上皮转化（MET）而抑制HS；高通量测序分析显示miR-200家族成员（miR-200s）在ESCs中高表达而在HSF中低表达；分子生物学检测发现miR-200s的主要靶基因ZEB在ESCs和正常皮肤低表达而在HSF和HS中高表达。据此，我们提出“ESCs-Exo通过传递miR-200s负调控ZEB，诱导HSF发生MET进而抑制HS”的科学假设。本项目拟采用质粒转染、miRNA海绵及siRNA干扰等技术，通过裸鼠人HS移植模型和体外细胞学研究，深入探讨ESCs-Exo诱导HSF发生MET的具体机制。研究成果有望揭示ESCs-Exo抑制HS的关键机制，推动ESCs-Exo的临床应用，并为治疗HS提供新的线索与理论依据。

The overproduction of hypertrophic scar fibroblasts (HSF) caused by excessive epithelial-mesenchymal transition (EMT) is one of the most critical factors leading to hypertrophic scar (HS). Our previous studies confirmed that epidermal stem cells (ESCs) could induce the mesenchymal-epithelial transformation (MET) of HSF mainly by exosomes (Exo); high-throughput sequencing analysis showed high expression of miR-200 family members (miR-200s) in ESCs and low expression in HSF; molecular biology examines discovered that ZEB, the major target gene of miR-200s, was low-expressed in ESCs and healthy skin but high-expressed in HSF and HS. Therefore, we hypothesized that ESCs-Exo delivered miR-200s to induce the MET of HSF and inhibit HS by negatively regulating ZEB. Taken together, this project intends to clarify the mechanism of the MET of HSF induced by ESCs-exosomes, and provide the new theoretical basis and clues for the treatment of HS.