KC细胞介导创面再上皮化是创面正常愈合的关键环节，而难愈创面创缘KC细胞常呈现过度增殖，但移行和上皮化障碍，目前机制不清。前期预实验证实，HDAC2敲除的KC细胞迁移增加,呈现EMT表型，EMT标记分子E-钙粘蛋白表达下降，Zeb1表达上调，同时EMT正性调控分子H19表达显著上调。另外，HDAC2于创面愈合过程中呈时空性表达，并受TGF-β（创面愈合、上皮化及EMT的重要调控分子）所调控。为此，我们提出"HDAC2通过直接阻遏H19的表达，负性调控KC细胞EMT，并协同TGF-β信号时空性介导KC细胞的EMT/MET进程，有效调控创面再上皮化和愈合"的机制假设。为证实此假设，本研究拟应用HDAC2敲除及GFP标记的KC细胞，从细胞和动物层面通过系列生物学实验，探索TGF-β-HDAC2-H19信号轴对KC细胞EMT/MET和创面再上皮化的作用机制，为发展难愈创面的治疗新策略提供理论依据。

Keratinocyte (KC) EMT plays an important role in wound re-epithelialization, a key process of normal wound healing, however hyperproliferative and nonmigratory Keratinocyte shows in the Margin area of chronic wounds, which impairs wound re-epitheliazation, but its molecular mechanism remains largely unclear. Our preliminary studies demonstrated that HDAC2-knockout KC cells showed increased migration and EMT features, such as decreased E-cadherin and increased Zeb1. It was found that LncRNA-H19, a positive regulator of EMT, was significantly upregulated in HDAC2-knockout KC cells. On the other hand, the special and temporal expression of HDAC2 during wound healing was proved to be regulated by TGF-β, a factor known to be involved in wound healing, re-epithelialization, and EMT. So, we speculated that, HDAC2 may negatively regulate EMT of KCs by downregulating H19, and together with TGF-β, mediate spatial and temporal regulation of EMT/MET of KCs to promote wound re-epithelialization and wound healing. To confirm this hypothesis, this study intends to investigate how the TGF-β-HDAC2-H19 signaling axis regulate EMT of KCs to mediate wound re-epithelialization, which shall expand our understanding of wound epithelization and inspire new treatment strategy.