Wnt-associated Dkk3 in inflammatory and fibrosing skin disease (C06)

Wnt 相关 Dkk3 在炎症和纤维化皮肤病中的作用 (C06)

• 批准号: 426035288
• 金额: --
• 依托单位: Abteilung Zelluläre und Molekulare Pathologie
• 依托单位国家: 德国
• 项目类别: CRC/Transregios
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/426035288?language=en
• 关键词: Wnt; associated; Dkk3; inflammatory; fibrosing

Radiation dermatitis can initiate a chronic inflammatory/fibrosing process. We found that Dickkopf-3 (Dkk3), a Wnt-related protein linked to immune regulation, promotes chronic fibrosing inflammation in mouse models of radiation damage. Dkk3 knockouts do not develop epidermal hyperplasia, or chronic dermal fibroblast/inflammatory activation. The proposal seeks to (i) identify the relevant cellular source of Dkk3 in radiation damaged skin using reporter mice and targeted Dkk3 knockouts, (ii) characterize Dkk3 effects on local macrophages and T cells, (iii) dissect the impact of Dkk-related signalling pathways using human skin models, and (iv) connect radiation-induced epigenetic modifications to expression of Dkk3 and chronic inflammatory fibrosis.

放射性皮炎可引发慢性炎症/纤维化过程。我们发现Dickkopf-3（Dkk 3），一种与免疫调节相关的Wnt相关蛋白，在辐射损伤的小鼠模型中促进慢性纤维化炎症。Dkk 3敲除不发生表皮增生或慢性真皮成纤维细胞/炎症活化。该提案旨在（i）使用报告小鼠和靶向Dkk 3敲除来鉴定辐射损伤皮肤中Dkk 3的相关细胞来源，（ii）表征Dkk 3对局部巨噬细胞和T细胞的作用，（iii）使用人类皮肤模型剖析Dkk相关信号传导途径的影响，以及（iv）将辐射诱导的表观遗传修饰与Dkk 3的表达和慢性炎性纤维化联系起来。