SNX16 aggravates AngII-induced cardiac hypertrophy in mice via EGFR transactivation
Cardiac hypertrophy is an independent risk factor for heart failure (HF) which often leads to cardiovascular disease-related death worldwide. Here we show that the upregulated expressions of Sorting Nexin 16 (SNX16) are evident in the hypertrophic hearts. Cardiac-specific deletion of SNX16 significantly inhibited AngII-induced cardiac hypertrophy and cardiomyocytic enlargement in male mice. In addition, we observed that both AngII stimulation and SNX16 overexpression markedly enlarged cardiomyocytes and promoted EGFR transactivation, and these effects were almost completely abolished by AZD9291, an inhibitor of the EGFR pathway. SNX16 deficiency significantly inhibited AngII- or EGF-induced recycling of EGFR in endosomal trafficking in cardiomyocytes. Finally, the elevated expression of SNX16 and the phosphorylation of EGFR and Src were further confirmed in heart tissues from patients with cardiac hypertrophy. Therefore, the present study demonstrates that SNX16-mediated transactivation of EGFR plays a key role in AngII-induced cardiac hypertrophy via enhancing the recycling of EGFR.
Authors
- Xiaoyong Ren (ORCID: https://orcid.org/0000-0002-0237-6103)
- Yinuo Zeng (ORCID: https://orcid.org/0000-0002-9816-0920)
- Qikun Yang
- Lin Xie
- Yong Ji (ORCID: https://orcid.org/0000-0003-2650-5747)
- Yingjiong Lin (ORCID: https://orcid.org/0000-0003-3328-6925)
- Ke‐Yu Deng (ORCID: https://orcid.org/0000-0002-3519-6846)
- Xiao‐Feng Qiao (ORCID: https://orcid.org/0000-0002-7841-3812)
- Xin Li (ORCID: https://orcid.org/0000-0002-9466-2659)
- Xiaolei Wang (ORCID: https://orcid.org/0000-0003-3403-1174)
- Lu Chen (ORCID: https://orcid.org/0000-0001-8380-014X)
- Bin Lü (ORCID: https://orcid.org/0000-0003-3984-6380)
- Jing He (ORCID: https://orcid.org/0000-0003-3904-8928)
- Guan-Hui Yu
- Xin Wu (ORCID: https://orcid.org/0000-0002-3839-4768)
- Hong‐Bo Xin (ORCID: https://orcid.org/0000-0002-4257-207X)
- Lulu Hu (ORCID: https://orcid.org/0000-0002-2008-3996)
- Ke Wen
Institutions
- Nanchang University (CN)
- Shaanxi Provincial People's Hospital (CN)
- First Affiliated Hospital of Jiangxi Medical College (CN)
- Jiangxi Provincial People's Hospital (CN)
- Nanjing Medical University (CN)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-11-29
- DOI
- https://doi.org/10.1038/s42003-025-09243-w
- Primary Topic
- Cardiac electrophysiology and arrhythmias
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Jiangxi Province
- Nanchang University
- Health Commission of Jiangxi Province
- National Key Research and Development Program of China