项目名称: Fra-1抑制角质形成细胞糜烂性毒物损伤后炎性因子释放及对核增殖抗原PCNA调控的作用与机制研究
项目编号: No.81502711
项目类型: 青年科学基金项目
立项/批准年度: 2016
项目学科: 医药、卫生
项目作者: 叶枫
作者单位: 中国人民解放军第三军医大学
项目金额: 18万元
中文摘要: 皮肤在糜烂性毒物损伤后恢复缓慢,与角质形成细胞损伤有关。MAPK下游的p38与ERK1/2通路据报道参与了染毒后细胞增殖抑制,炎性因子释放等作用。Fra-1是ERK1/2下游的调控因子,FOS转录家族成员,在角质形成细胞高表达。毒物损伤后Fra-1的表达变化及作用不明。我们前期实验表明,角质形成细胞染毒后Fra-1丢失,增殖核抗原PCNA降低,细胞炎性反应因子COX-2增加。结合RNAi干扰沉默Fra-1,EGF刺激增加Fra-1,我们发现:1.Fra-1正向调控PCNA;2. Fra-1抑制染毒细胞COX-2增加;3. Fra-1过表达抑制染毒细胞PCNA含量。我们推测,染毒细胞Fra-1降低有抑制增殖和促炎性因子释放的作用,Fra-1过表达可以抑制炎性反应引起的PCNA增加。对Fra-1,炎性反应与PCNA三者间调控关系的深入研究将为糜烂性毒物损伤皮肤的复杂机制提供新的认识。
中文关键词: 细胞增殖;干细胞;信号通路;转录因子
英文摘要: Mustard gas, an Alkylation agent, specifically damage basal cells and cause blistering and delayed healing. The changes of p38-ERK signaling pathway was reported to be involved in cell inflammation, proliferation, and differentiation. Fra-1, a FOS transcription family members, is a downstream regulator of ERK1/2, expressed in many tissues. In the skin, it specifically expressed in basal cells. Our previous results find that the expression of Fra-1 was lost after SM exposure both in cell culture and in hairless mouse skin. Although Fra-1 was reported to have a broad function, like proliferation, inflammation regulation, cytokine secretion, interstitial conversion effect, but little report was about its function in stress response after skin damage. By employing RNAi interference, Western Blotting and other methods, we showed that the proliferation were significantly affected and inflammation response was activated after SM exposure. The loss of Fra-1 directly decrease the expression of PCNA and Fra-1 act as anti-inflammation in SM exposure model which negatively regulate PCNA expression. The mechanism study of the relationship between Fra-1, PCNA and inflammatory response will provide new understanding of mustard skin lesion.
英文关键词: Cell Proliferation;Stem cells;Signal pathway;Transcription factor