角质形成细胞表达RIG-I在皮肤创伤愈合过程中的作用及其机制研究

表皮角质形成细胞分裂增殖是皮肤创伤愈合的关键环节，其增殖能力不足会引起创伤再上皮化受阻，最终导致创伤经久不愈，即慢性创伤。目前，创伤愈合过程中，调控角质形成细胞分裂增殖的机制并不十分清楚。我们前期研究结果证明：RIG-I在皮肤创伤表皮角质形成细胞中的表达增高并受到炎症因子IFN-γ的调控，RIG-I能够促进表皮角质形成细胞分裂增殖且RIG-I基因剔除小鼠皮肤创伤愈合速度显著减慢，但RIG-I促进角质形成细胞分裂增殖以及创伤愈合的分子机制尚不明确。本项目将从临床患者、动物模型及细胞实验着手，以期明确：①慢性创伤如糖尿病足中，RIG-I的表达相对于正常创伤是否降低；②RIG-I促进角质形成细胞分裂增殖以及创伤愈合的具体机制；③RIG-I的激动剂能否用于临床上慢性创伤的治疗。本项目的研究不仅能够明晰RIG-I在皮肤中的免疫调节功能，同时也能为临床上慢性创伤的治疗提供依据。

Epidermal keratinocyte proliferation is an essential process of wound repair and diminished keratinocyte proliferation leads to impaired epidermal re-epithelialization, eventually leading to chronic wounds. At present, the mechanisms that regulate epithelial proliferation are incompletely understood. Our previous data show that RIG-I expression is significantly increased in epidermal keratinocyte of skin wounds and upregulated by IFN-γ. Moreover, RIG-I could promote epidermal keratinocyte proliferation and RIG-I-/- mice exhibit delayed wound healing when compared to WT mice. However, the mechanisms by which RIG-I promotes keratinocyte proliferation and wound healing remain largely unknown. In this study, we will identify whether the expression of RIG-I in chronic wounds such as diabetic foot is decreased when compared to normal wounds and explore the underling mechanisms of RIG-I in promoting keratinocyte proliferation and wound healing. What's more, we will also make it clear that whether the agonist of RIG-I could be used in the treatment of chronic wounds. This project will not only clarify the immunomodulatory effect of RIG-I in skin, but also provide evidence for the clinical treatment of chronic wounds.