Ubiquitin Specific Protease 9X Regulates the Activation of ARK5 and Promotes Progression of Fibrotic Remodeling

IF 8.4 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC: Basic to Translational Science Pub Date : 2025-07-01 DOI:10.1016/j.jacbts.2025.02.014

Xuelian Li MM , Shijiu Jiang MD , Wenling Yang MM , Xianjie Zhu MM , Fan Zhang MM , Zhiyang Li MM , Xiaopeng Guo MD, PhD , Yumiao Wei MD, PhD

引用次数: 0

Abstract

USP9X plays a crucial role in myocardial fibrosis. This study showed increased USP9X expression in myocardial infarction models, associated with collagen deposition and myofibroblast activation. Myofibroblast-specific USP9X knockout and pharmacologic inhibition with Degrasyn both reduced fibrosis and improved cardiac function. Mechanistically, USP9X was found to bind and deubiquitinate AMPK-related kinase 5, thereby activating it and promoting transforming growth factor-β1–induced myofibroblast transformation via the Rho kinase pathway. These findings highlight USP9X as a potential therapeutic target for fibrotic diseases.

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泛素特异性蛋白酶9X调节ARK5的激活并促进纤维化重塑的进展。

USP9X在心肌纤维化中起关键作用。该研究显示心肌梗死模型中USP9X表达增加，与胶原沉积和肌成纤维细胞活化有关。肌成纤维细胞特异性USP9X基因敲除和Degrasyn药物抑制均可减少纤维化并改善心功能。在机制上，USP9X被发现与ampk相关的激酶5结合并去泛素化，从而激活它，并通过Rho激酶途径促进转化生长因子-β1诱导的肌成纤维细胞转化。这些发现强调了USP9X作为纤维化疾病的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

JACC: Basic to Translational Science CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

14.20

自引率

1.00%

发文量

161

审稿时长

16 weeks

期刊介绍： JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.