Abstract：
Cutaneous wound healing is a challenge in plastic and reconstructive surgery. In theory, cells undergoing mesenchymal transition will achieve re-epithelialization through mesenchymal-epithelial transition at the end of wound healing. But in fact, some pathological stimuli will inhibit this biological process and result in scar formation. If mesenchymal-epithelial transition can be activated at the corresponding stage, the ideal wound healing may be accomplished. Two in vivo skin defect mouse models and dermal-derived mesenchymal cells were used to evaluate the effect of lithium chloride in wound healing. The mesenchymal-epithelial transition was detected by immunohistochemistry staining. In vivo, differentially expressed genes were analysed by transcriptome analyses and the subsequent testing was carried out. We found that lithium chloride could promote murine cutaneous wound healing and facilitate mesenchymal-epithelial transition in vivo and in vitro. In lithium chloride group, scar area was smaller and the collagen fibres are also orderly arranged. The genes related to mesenchyme were downregulated and epithelial mark genes were activated after intervention. Moreover, transcriptome analyses suggested that this effect might be related to the inhibition of CXCL9 and IGF2, subsequent assays demonstrated it. Lithium chloride can promote mesenchymal-epithelial transition via downregulating CXCL9 and IGF2 in murine cutaneous wound healing, the expression of IGF2 is regulated by β-catenin. It may be a potential promising therapeutic drug for alleviating postoperative scar and promoting re-epithelialization in future.
摘要：
皮肤伤口愈合在整形和重建手术中是一个挑战。理论上,经历间充质转化的细胞将在伤口愈合结束时通过间充质-上皮转化实现再上皮化。但事实上,一些病理刺激会抑制这种生物过程并导致瘢痕形成。如果间质-上皮转化可以在相应阶段被激活，可以实现理想的伤口愈合。使用两种体内皮肤缺损小鼠模型和真皮来源的间充质细胞来评估氯化锂在伤口愈合中的作用。免疫组化染色检测间质-上皮转化。在体内,通过转录组分析分析差异表达的基因，并进行随后的测试。我们发现氯化锂可以促进小鼠皮肤伤口的愈合，并促进体内和体外的间充质-上皮转化。在氯化锂组中，瘢痕面积较小，胶原纤维排列有序。干预后，间充质相关基因下调，上皮标记基因被激活。此外，转录组分析表明，这种作用可能与CXCL9和IGF2的抑制有关，随后的实验证明了这一点。氯化锂可以通过下调CXCL9和IGF2促进小鼠皮肤伤口愈合的间质-上皮转化，IGF2的表达受β-catenin调节。它可能是减轻术后瘢痕和促进上皮再形成的潜在有希望的治疗药物。
