瘢痕疙瘩
心理压抑
细胞外基质
细胞生物学
下调和上调
转录因子
信号转导
内部收益率1
基因表达调控
癌症研究
化学
基因表达
生物
基因
医学
生物化学
病理
作者
Jingjing Gu,Chang‐Mi Deng,Qing‐Lan Feng,Jun Li,Dingheng Zhu,Qing Cheng,Zhili Rong,Bin Yang
标识
DOI:10.1016/j.jid.2023.01.008
摘要
Keloids represent a fibrotic disorder characterized by the excessive deposition of extracellular matrix (ECM). However, the mechanisms through which ECM deposition in keloids is regulated remain elusive. In this study, we found that the expression of both TWEAK and its cognate receptor Fn14 was significantly downregulated in keloids and that TWEAK/Fn14 signaling repressed the expression of ECM-related genes in keloid fibroblasts. The IRF1 gene was essential for this repression, and the TWEAK/Fn14 downstream transcription factor p65 directly bound to the promoter of the IRF1 gene and induced its expression. Furthermore, in patients with keloid, the expression of TWEAK and Fn14 was negatively correlated with that of ECM genes and positively correlated with that of IRF1. These observations indicate that relief of TWEAK/Fn14/IRF1-mediated ECM deposition repression contributes to keloid pathogenesis, and the identified mechanism and related molecules provide potential targets for keloid treatment in the future.
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