TPM1-p.E181K mutation suppresses CaMKII/HDAC4 signaling pathway leading to pediatric restrictive cardiomyopathy
This study establishes a novel link between TPM1-p.E181K and sporadic RCM. We demonstrate that its pathogenesis is mediated through a cascade of events: calcium dyshomeostasis leads to the suppression of CaMKII/HDAC4 phosphorylation, which subsequently causes sarcomere structural disruption, and ultimately results in myocardial hypercontractility. This identified signaling axis may represent a promising therapeutic target for RCM.
Authors
- Kun Xia
- Xiaoyuan Feng
- Ruoshu Wang
- Dongming Sun
- William W. Yu (ORCID: https://orcid.org/0000-0001-5354-6718)
- Jia Fu
- Youxian Zhang
- Aiguo Zhai
- Yufeng Huang
- Jing Zhang
- Xiaobin Li
- Yong Zhang
Institutions
- Xi'an University of Science and Technology (CN)
- Wuhan University (CN)
- Integrated Chinese Medicine (China) (HK)
- Zhongnan Hospital of Wuhan University (CN)
- Wuhan Children's Hospital (CN)
- Shanxi Science and Technology Department (CN)
- Huazhong University of Science and Technology (CN)
Publication Details
- Journal
- Frontiers in Genetics
- Published
- 2026-01-06
- DOI
- https://doi.org/10.3389/fgene.2025.1654907
- Primary Topic
- Histone Deacetylase Inhibitors Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Wuhan University
- Zhongnan Hospital of Wuhan University