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

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

doi:10.1016/j.isci.2023.107888

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

iScience. 2023 Sep 9;26(10):107888. doi: 10.1016/j.isci.2023.107888. eCollection 2023 Oct 20.

Authors

Tianyu Li^{1

2}, Xue Xiong¹, Yujing Wang¹, Yue Li¹, Yao Liu¹, Mingxiu Zhang¹, Chao Li¹, Tong Yu³, Wei Cao⁴, Shuangshuang Chen¹, Huizhen Zhang¹, Xiaona Wang¹, Lifang Lv⁵, Yuhong Zhou¹, Haihai Liang^{1

6}, Xuelian Li¹, Hongli Shan^{1

3}

Affiliations

¹ Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
² Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P.R. China.
³ Shanghai Frontiers Science Research Center for Druggability of Cardiovascular Noncoding RNA, Institute for Frontier Medical Technology, Shanghai University of Engineering Science, Shanghai 201620, P.R. China.
⁴ Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
⁵ The Centre of Functional Experiment Teaching, School of Basic Medicine, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
⁶ Research Unit of Noninfectious Chronic Diseases in Frigid Zone (2019RU070), Chinese Academy of Medical Sciences, Harbin 150081, P.R. China.

Abstract

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-β1, suggesting that NET1 was involved in the pathological process of cardiac fibrosis. Overexpression of NET1 promoted β-catenin expression in the nucleus and significantly increased the proliferation and migration of cardiac fibroblasts. NET1 may form a complex with β-catenin through GSK3β. Knockdown of β-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 β-catenin, α-SMA, and collagen content induced by MI. In conclusion, NET1 may regulate the activation of Wnt/β-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.

Keywords: Biochemistry; Biological sciences; Cell biology; Molecular biology.