Endothelial TBK1 Deficiency Inhibits Endothelial-to-Mesenchymal Transition and Atherogenesis Through Suppressing PAK1/ERK1/2 Signaling
The interaction between activated TBK1 and PAK1IP1 inhibits the binding of PAK1IP1 to PAK1, which, in turn, increases the phosphorylation of PAK1 and ERK1/2 in endothelial cells. This process drives EndMT. Endothelium-specific TBK1 knockdown or GSK8612 treatment inhibits EndMT and plaque formation. Safe TBK1 inhibitors could be developed into effective agents for the treatment of atherosclerotic vascular disease.
Authors
- Gang Fan (ORCID: https://orcid.org/0000-0003-1894-3253)
- Xiang Cheng (ORCID: https://orcid.org/0000-0002-7298-1800)
- Juan Huang (ORCID: https://orcid.org/0000-0003-1477-2602)
- Yujie Pu
- Peihua Dong (ORCID: https://orcid.org/0009-0003-8540-2753)
- Qing Chen (ORCID: https://orcid.org/0000-0002-2191-6558)
- Lei He (ORCID: https://orcid.org/0000-0002-3821-2047)
- Chenglin Zhang (ORCID: https://orcid.org/0000-0003-1063-0199)
- Yu-Tsung Shih
- Chak Kwong Cheng
- Jiang-Yun Luo
- Ronald Ching Wan Ma
- Yu Huang
- Li Wang
- Chi Fai Ng
- Yandi Wu
- Zhong Zuo
- Jeng-Jinan Chiu
Institutions
- Department of Health (CN)
- National Health Research Institutes (TW)
- City University of Hong Kong (HK)
- Chinese University of Hong Kong (HK)
- Tung Wah Hospital (CN)
- City University of Hong Kong, Shenzhen Research Institute (CN)
- Wuhan Union Hospital (CN)
- Union Hospital (US)
- Union Hospital (CN)
- Taipei Medical University (TW)
- Tianjin Medical University (CN)
Publication Details
- Journal
- Circulation Research
- Published
- 2026-02-13
- DOI
- https://doi.org/10.1161/circresaha.125.326815
- Primary Topic
- Congenital heart defects research
- Type
- article
- Field-Weighted Citation Impact
- 0.00