Clusterin, through exercise-mediated liver-heart crosstalk, promotes heart regeneration after myocardial infarction
Abstract
Loss of cardiomyocytes drives cardiac remodeling and ultimately leads to heart failure, highlighting the need to promote cardiac regeneration. Exercise has been known to enhance cardiac repair and stimulate cardiomyocyte proliferation; however, the underlying mechanisms remain unclear. In this study, we demonstrated that exercise-induced exerkine clusterin mediates the pro-regenerative effects of running plasma on cardiac repair and cardiomyocyte proliferation following myocardial infarction (MI). Cardiac-specific Clu knockout attenuated, whereas clusterin overexpression enhanced, post-MI cardiac regeneration. Recombinant clusterin administration promoted heart regeneration in adult mice after MI. Mechanistically, clusterin activated NF-κB via proteasome-dependent IκBα degradation through direct binding with IκBα. Furthermore, the liver was identified as the major source of exercise-induced circulating clusterin; hepatocyte-specific Clu knockdown abolished the stimulatory effect of exercise plasma on cardiac regeneration. This study reveals a liver-heart crosstalk mechanism by which exercise-induced clusterin promotes cardiomyocyte proliferation, positioning clusterin as a potential therapeutic target for post-MI heart failure.
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BibTeX
@article{wang2026clusterin,
title = {{Clusterin, through exercise-mediated liver-heart crosstalk, promotes heart regeneration after myocardial infarction}},
author = {Wei Wang and Feng Wang and Yanji He and Ye Zhang and Chao Li and Xiaokang Chen and Xuewei Xia and Yunchang Liu and Lu Zhou and Zegang Hu and Zhuxin Li and Jing Wang and Liangpeng Li and Chunyu Zeng and Gengze Wu},
journal = {Cell Reports},
year = {2026},
month = oct,
doi = {10.1016/j.celrep.2026.118234},
url = {https://linkinghub.elsevier.com/retrieve/pii/S2211124726013136},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Clusterin, through exercise-mediated liver-heart crosstalk, promotes heart regeneration after myocardial infarction
AU - Wei Wang
AU - Feng Wang
AU - Yanji He
AU - Ye Zhang
AU - Chao Li
AU - Xiaokang Chen
AU - Xuewei Xia
AU - Yunchang Liu
AU - Lu Zhou
AU - Zegang Hu
AU - Zhuxin Li
AU - Jing Wang
AU - Liangpeng Li
AU - Chunyu Zeng
AU - Gengze Wu
PY - 2026
DA - 2026/10/31
JO - Cell Reports
DO - 10.1016/j.celrep.2026.118234
UR - https://linkinghub.elsevier.com/retrieve/pii/S2211124726013136
AB - Loss of cardiomyocytes drives cardiac remodeling and ultimately leads to heart failure, highlighting the need to promote cardiac regeneration. Exercise has been known to enhance cardiac repair and stimulate cardiomyocyte proliferation; however, the underlying mechanisms remain unclear. In this study, we demonstrated that exercise-induced exerkine clusterin mediates the pro-regenerative effects of running plasma on cardiac repair and cardiomyocyte proliferation following myocardial infarction (MI). Cardiac-specific Clu knockout attenuated, whereas clusterin overexpression enhanced, post-MI cardiac regeneration. Recombinant clusterin administration promoted heart regeneration in adult mice after MI. Mechanistically, clusterin activated NF-κB via proteasome-dependent IκBα degradation through direct binding with IκBα. Furthermore, the liver was identified as the major source of exercise-induced circulating clusterin; hepatocyte-specific Clu knockdown abolished the stimulatory effect of exercise plasma on cardiac regeneration. This study reveals a liver-heart crosstalk mechanism by which exercise-induced clusterin promotes cardiomyocyte proliferation, positioning clusterin as a potential therapeutic target for post-MI heart failure.
SN - 2211-1247
ER -