湖南师范大学邓云研究组近日取得一项新成果。经过不懈努力，他们发现了在斑马鱼中，lim1的缺失通过激活gp130/Jak1/Stat3通路导致心脏重构异常和心力衰竭。相关论文于2025年4月17日发表在《遗传学报》杂志上。

该研究团队将探讨LIMS1在心脏重塑和心力衰竭中的功能和机制。该课题组在扩张型心肌病（DCM）患者和小鼠心肌细胞中发现了LIMS1表达升高，表明LIMS1失调有助于心脏病理。利用CRISPR/Cas9技术，研究团队建立了lims1功能缺失突变体的斑马鱼模型，该模型表现出严重的心室重构、收缩功能障碍和过早死亡，证明了lims1在维持心脏完整性方面的重要作用。转录组学分析揭示了gp130/Jak1/Stat3信号在lims1缺陷心脏中的激活。引人注目的是，Stat3或c-Fos的药理学抑制部分地挽救了心肌病表型。他们的发现通过gp130/Jak1/Stat3过度激活揭示了lim1缺陷心衰的潜在机制，为心脏重塑和潜在的治疗策略提供了见解。

据介绍，LIM锌指结构域1 （LIMS1）是一种进化保守的LIM结构域衔接蛋白，涉及多种病理，包括癌症和神经系统疾病。然而，其在心脏疾病中的作用及其潜在机制尚不清楚。

附：英文原文

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

Author: Yonghe Ding f, Yun Deng a

Issue&Volume: 2025/04/17

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.

DOI: 10.1016/j.jgg.2025.04.003

Source: https://www.sciencedirect.com/science/article/pii/S1673852725001122