Loss of <i>lims1</i> causes aberrant cardiac remodeling and heart failure via activating gp130/Jak1/Stat3 pathway in zebrafish

Wuming Qin; Xiaobo Yang; Lu Zhang; Linghui Cao; Shi Ouyang; Dafeng Yang; Yangzhao Zhou; Anji Chen; Tao Liao; Xinyu Zhu; Yuting Liu; Wei Tang; Tongtong Ma; Yiyue Tang; Yonghe Ding; Yun Deng

doi:10.1016/j.jgg.2025.04.003

Volume 52 Issue 12

Dec. 2025

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Loss of lims1 causes aberrant cardiac remodeling and heart failure via activating gp130/Jak1/Stat3 pathway in zebrafish

doi: 10.1016/j.jgg.2025.04.003

a. Laboratory of Zebrafish Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China;
b. Department of Clinical Laboratory, Qingdao Women's and Children's Hospital, Qingdao, Shandong 266034, China;
c. The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan 410004, China;
d. Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China;
e. Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Changsha, Hunan 410007, China;
f. The Affiliated Hospital of Qingdao University & Biomedical Sciences Institute, Qingdao Medical College of Qingdao University, Qingdao, Shandong 266021, China

Funds:

We thank all the members of the Zebrafish Genetics Laboratory at Hunan Normal University for their assistance. We thank the National Natural Science Foundation of China (82070394, 82371863, 31970504, 82100491, and 82000307) and the Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control project (HPKL2023001) for their support of this research.

Received Date: 2024-12-13
Accepted Date: 2025-04-07
Rev Recd Date: 2025-04-04
Publish Date: 2025-12-31

Abstract

Abstract

LIM zinc finger domain containing 1 (LIMS1), an evolutionarily conserved LIM domain adaptor protein, is implicated in diverse pathologies, including cancer and neurological disorders. However, its roles in cardiac diseases and the underlying mechanisms remain unclear. Here, we explore the functions and mechanisms of LIMS1 in cardiac remodeling and heart failure. We identify the elevated LIMS1 expression in patients with dilated cardiomyopathy and murine cardiomyocytes, suggesting that LIMS1 dysregulation contributes to cardiac pathology. Using CRISPR/Cas9 technology, we generate a zebrafish model of lims1 loss-of-function mutant, which exhibits severe cardiac chamber remodeling, systolic dysfunction, and premature mortality, demonstrating the essential role of lims1 in maintaining cardiac integrity. Transcriptomic profiling reveals the activation of the gp130/Jak1/Stat3 signaling in the lims1-deficient hearts. Strikingly, pharmacological inhibition of Stat3 or c-Fos partially rescues cardiomyopathy phenotypes. Our findings reveal the underlying mechanism of lims1 deficiency-caused heart failure through gp130/Jak1/Stat3 hyperactivation, offering insights into cardiac remodeling and potential therapeutic strategies.
- lims1,
- Cardiac remodeling,
- Heart failure,
- gp130/Jak1/Stat3 pathway,
- Zebrafish

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References(35)

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