Wnt5a/Ca2+ signal promotes myogenic differentiation by mediating a slow and sustained influx of Ca2+
6 affiliations
- 1Department of Rehabilitation Medicine, First Affiliated Hospital of Gannan Medical University, 128 Jinling Road, Zhanggong District, Ganzhou, 341000 Jiangxi China
- 2Ganzhou Key Laboratory of Rehabilitation Medicine, Ganzhou, China
- 3School of Basic Medicine, Gannan Medical University, Ganzhou, China
- 4Ganzhou Intelligent Rehabilitation Technology Innovation Center, Ganzhou, China
- 5First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- 6Department of Oncology, First Affiliated Hospital of Gannan Medical University, 128 Jinling Road, Zhanggong District, Ganzhou, 341000 Jiangxi China
Abstract
The extracellular Ca2+ is crucial for the regeneration of skeletal muscles, but there is still uncertainty regarding the channels through which it enters the cells. The purpose of this study is to investigate how the Wnt5a/Ca²⁺ signaling pathway promotes myogenic differentiation by regulating which calcium channels on the cell membrane. Myogenic regulatory factors (MRFs) play an important regulatory role in the occurrence and development of skeletal muscle, while overexpression or knockdown of Wnt5a can affect the expression levels of MRFs. Increased expression of Wnt5a resulted in significant increase of intracellular Ca2+ levels, and knockdown of TRPC3 could partially reverse the effect of Wnt5a. This indicates that in addition to the TRPC3 channel, there are other Ca2+ channels involved in the process of transporting extracellular Ca2+ into the cells. When we treated with verapamil, we found that it could significantly reduce the level of Ca2+ entering the cells, indicating that this unknown Ca2+ channel is a slow calcium channel. Through co-immunoprecipitation, we found that CaV1.1 was abundantly accumulated in the TRPC3 pull-down complex, indicating that this slow calcium channel is CaV1.1, and the expression of CaV1.1 is influenced by TRPC3. In simple terms, the activated TRPC3 activates Cav1.1, inducing a slow and sustained inward flow of extracellular Ca2+, leading to the increase of intracellular levels of Ca2+, and finally promote myogenic differentiation.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13287-026-05218-8.
Related
- Role of calcineurin B homologous protein 3 in C2C12 myogenic differentiation
- KDM5A overexpression modulates key myogenic differentiation factors and sarcomere gene expression.
- Molecular Mechanisms Implicated in Myogenic Differentiation of Human Alveolar Mucosa-Derived Cells.
- Tamoxifen Promotes Sustained Bifidobacterium Enrichment in the Gut Microbiota of Male and Female Rats After Spinal Cord Injury
- RBFOX2 Autoregulation Promotes Cardiomyocyte Transcriptome Maturation and Differentiation
BibTeX
@article{wang2026wnt5aca2,
title = {{Wnt5a/Ca2+ signal promotes myogenic differentiation by mediating a slow and sustained influx of Ca2+}},
author = {Mao-yuan Wang and Jin-guo Cao and Yan-biao Zhong and Yun Luo and Fu-hua Xie and Mei-xuan Zou and Wen-juan Wu and Xin-ye Ouyang and Jia-ming Yang and Rui-lian Xie},
journal = {Stem Cell Research \& Therapy},
year = {2026},
month = aug,
doi = {10.1186/s13287-026-05218-8},
url = {https://doi.org/10.1186/s13287-026-05218-8},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Wnt5a/Ca2+ signal promotes myogenic differentiation by mediating a slow and sustained influx of Ca2+
AU - Mao-yuan Wang
AU - Jin-guo Cao
AU - Yan-biao Zhong
AU - Yun Luo
AU - Fu-hua Xie
AU - Mei-xuan Zou
AU - Wen-juan Wu
AU - Xin-ye Ouyang
AU - Jia-ming Yang
AU - Rui-lian Xie
PY - 2026
DA - 2026/08/07
JO - Stem Cell Research & Therapy
DO - 10.1186/s13287-026-05218-8
UR - https://doi.org/10.1186/s13287-026-05218-8
AB - The extracellular Ca2+ is crucial for the regeneration of skeletal muscles, but there is still uncertainty regarding the channels through which it enters the cells. The purpose of this study is to investigate how the Wnt5a/Ca²⁺ signaling pathway promotes myogenic differentiation by regulating which calcium channels on the cell membrane. Myogenic regulatory factors (MRFs) play an important regulatory role in the occurrence and development of skeletal muscle, while overexpression or knockdown of Wnt5a can affect the expression levels of MRFs. Increased expression of Wnt5a resulted in significant increase of intracellular Ca2+ levels, and knockdown of TRPC3 could partially reverse the effect of Wnt5a. This indicates that in addition to the TRPC3 channel, there are other Ca2+ channels involved in the process of transporting extracellular Ca2+ into the cells. When we treated with verapamil, we found that it could significantly reduce the level of Ca2+ entering the cells, indicating that this unknown Ca2+ channel is a slow calcium channel. Through co-immunoprecipitation, we found that CaV1.1 was abundantly accumulated in the TRPC3 pull-down complex, indicating that this slow calcium channel is CaV1.1, and the expression of CaV1.1 is influenced by TRPC3. In simple terms, the activated TRPC3 activates Cav1.1, inducing a slow and sustained inward flow of extracellular Ca2+, leading to the increase of intracellular levels of Ca2+, and finally promote myogenic differentiation. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13287-026-05218-8.
SN - 1757-6512
ER -