转录因子Meox1协同染色质重塑因子CHD1调控P311表达促进瘢痕形成的分子机制研究

批准号:
82002036
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
李海胜
依托单位:
学科分类:
烧伤与冻伤
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
李海胜
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中文摘要
烧伤等引起的皮肤增生性瘢痕是最常见的临床难题之一,但发病机制尚不完全清楚,致其防治效果有限。以往研究证实P311通过上调TGFβ1促进皮肤瘢痕形成,但其上游调控机制不详。我们前期发现TGFβ1可上调皮肤成纤维细胞P311表达,近来预实验初步发现转录因子Meox1及染色质重塑因子CHD1在TGFβ1诱导的P311表达中起着重要作用。据此,我们推测:TGFβ1通过上调转录因子Meox1的表达,将染色质重塑因子CHD1招募至P311启动子区,从而增加染色质开放性,二者协同促进P311转录和表达,导致瘢痕形成。本项目拟采用ChIP、reChIP、免疫共沉淀、染色质开放性分析、兔耳瘢痕模型、药物微针等证实这一设想。本项目的完成将发现一种Meox1和CHD1协同调控P311基因表达的新机制,完善P311和TGFβ1在增生性瘢痕中的正反馈调控模式,揭示增生性瘢痕发生新机理,为瘢痕防治提供新靶点和新线索。
英文摘要
Hypertrophic scar is a highly prevalent condition following burns and trauma wounds. However, the exact pathogenesis remains unclear and the therapeutic effect was poor and limited. Previous studies have confirmed that P311 could promote the hypertrophic scar formation through TGFβ1 signaling. However, the upstream regulatory mechanism of P311 expression remains unclear. Our preliminary research have confirmed that TGFβ1 could up-regulate the expression of P311 in skin fibroblasts, and found that transcription factor Meox1 and chromatin remodeler CHD1 might be the key regulators of TGFβ1-induced P311 gene expression. Based on the reported roles of Meox1 and CHD1 and our preliminary results, we hypothesize that TGFβ1 may regulate P311 gene transcription by recruiting the transcription factor Meox1 and chromatin remodeler CHD1, which could coordinate with each other to increase the P311 gene chromatin accessibility, and finally cause hypertrophic scar. To verify this hypothesis, we plan to use ChIP, re-ChIP, Co-Immunoprecipitation, chromatin accessibility analysis, rabbit ear hypertrophic scar model, drug-loaded microneedles and other techniques. Our research would clarify the novel mechanism of the regulation of P311 gene expression by Meox1 and CHD1 in the hypertrophic scar, which will support the positive feedback loop between P311 and TGFβ1 during hypertrophic scar formation. Therefore, our study will discover a new mechanism of hypertrophic scar formation and provide new targets and clues for the prevention and treatment of hypertrophic scar.
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DOI:10.2147/idr.s397051
发表时间:2023
期刊:Infection and drug resistance
影响因子:3.9
作者:
通讯作者:
DOI:10.1093/burnst/tkac056
发表时间:2023
期刊:BURNS & TRAUMA
影响因子:5.3
作者:Heng, Xue;Cai, Peng;Yuan, Zhiqiang;Peng, Yizhi;Luo, Gaoxing;Li, Haisheng
通讯作者:Li, Haisheng
DOI:10.3389/fcimb.2021.681731
发表时间:2021
期刊:Frontiers in cellular and infection microbiology
影响因子:5.7
作者:Gong Y;Peng Y;Luo X;Zhang C;Shi Y;Zhang Y;Deng J;Peng Y;Luo G;Li H
通讯作者:Li H
国内基金
海外基金
