Neuroepithelial cell-transforming 1 promotes cardiac fibrosis via the Wnt/8-catenin signaling pathway

作者：Li, Tianyu; Xiong, Xue; Wang, Yujing; Li, Yue; Liu, Yao; Zhang, Mingxiu; Li, Chao; Yu, Tong; Cao, Wei; Chen, Shuangshuang; Zhang, Huizhen; Wang, Xiaona; Lv, Lifang; Zhou, Yuhong; Liang, Haihai; Li, Xuelian^*; Shan, Hongli^*

来源：iScience, 2023, 26(10): 107888.

DOI：10.1016/j.isci.2023.107888

• EXCHANGE FACTOR NET1
• TARGETING WNT/BETA-CATENIN
• NUCLEOTIDE-EXCHANGE
• CARDIOMYOCYTES
• EXPRESSION
• PROTECTS
• INSIGHTS
• FAMILY
• GSK-3

This study found that the level of neuroepithelial cell-transforming gene 1 protein (NET1) was significantly increased in a mouse cardiac fibrosis model. Moreover, the expression level of NET1 was increased in cardiac fibrosis induced by TGF-beta 1, suggesting that NET1 was involved in the pathological process of cardiac fibrosis. Overexpression of NET1 promoted beta-catenin expression in the nucleus and significantly increased the proliferation and migration of cardiac fibroblasts. NET1 may form a complex with beta-catenin through GSK3b. Knockdown of beta-catenin alleviated the effects of NET1 overexpression on collagen production and cell migration. In the heart of NET1 knockout mice, NET1 knockout can reduce the expression of beta-catenin, alpha-SMA, and collagen content induced by MI. In conclusion, NET1 may regulate the activation of Wnt/beta-catenin and TGF/Smads signaling pathway, promote collagen synthesis in fibroblasts, and participate in cardiac fibrosis. Thus, NET1 may be a potential therapeutic target in cardiac fibrosis.

• 单位
  中国医学科学院; 哈尔滨医科大学