PUBLICATION
Loss of lims1 causes aberrant cardiac remodeling and heart failure via activating gp130/Jak1/Stat3 pathway in zebrafish
- Authors
- Qin, W., Yang, X., Zhang, L., Cao, L., Ouyang, S., Yang, D., Zhou, Y., Chen, A., Liao, T., Zhu, X., Liu, Y., Tang, W., Ma, T., Tang, Y., Ding, Y., Deng, Y.
- ID
- ZDB-PUB-250420-5
- Date
- 2025
- Source
- Journal of genetics and genomics = Yi chuan xue bao 52: 1600-1611 (Journal)
- Registered Authors
- Deng, Yun, Ding, Yonghe
- Keywords
- Cardiac remodeling, Heart failure, Zebrafish, gp130/Jak1/Stat3 pathway, lims1
- MeSH Terms
-
- Animals
- Cytokine Receptor gp130*/genetics
- Cytokine Receptor gp130*/metabolism
- Disease Models, Animal
- Heart Failure*/genetics
- Heart Failure*/metabolism
- Heart Failure*/pathology
- Humans
- Janus Kinase 1*/genetics
- Janus Kinase 1*/metabolism
- LIM Domain Proteins*/genetics
- LIM Domain Proteins*/metabolism
- Mice
- Myocytes, Cardiac/metabolism
- Myocytes, Cardiac/pathology
- STAT3 Transcription Factor*/genetics
- STAT3 Transcription Factor*/metabolism
- Signal Transduction
- Ventricular Remodeling*/genetics
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 40252966 Full text @ J. Genet. Genomics
Citation
Qin, W., Yang, X., Zhang, L., Cao, L., Ouyang, S., Yang, D., Zhou, Y., Chen, A., Liao, T., Zhu, X., Liu, Y., Tang, W., Ma, T., Tang, Y., Ding, Y., Deng, Y. (2025) Loss of lims1 causes aberrant cardiac remodeling and heart failure via activating gp130/Jak1/Stat3 pathway in zebrafish. Journal of genetics and genomics = Yi chuan xue bao. 52:1600-1611.
Abstract
LIM zinc finger domain containing 1 (LIMS1), an evolutionally 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 (DCM) 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping