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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进程。

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

作者信息

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

机构信息

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Department of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Graduate School of Dalian Medical University, Dalian, China.

出版信息

JACC Basic Transl Sci. 2025 Jul;10(7):101255. doi: 10.1016/j.jacbts.2025.02.014. Epub 2025 Apr 30.

DOI:10.1016/j.jacbts.2025.02.014
PMID:40310323
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12434208/
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.

摘要

USP9X在心肌纤维化中起关键作用。本研究表明，在心肌梗死模型中USP9X表达增加，这与胶原沉积和成肌纤维细胞活化有关。成肌纤维细胞特异性USP9X基因敲除以及使用Degrasyn进行药物抑制均可减少纤维化并改善心脏功能。从机制上讲，发现USP9X可结合并去泛素化AMPK相关激酶5，从而激活它，并通过Rho激酶途径促进转化生长因子-β1诱导的成肌纤维细胞转化。这些发现突出了USP9X作为纤维化疾病潜在治疗靶点的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f283/12434208/ed9f750c7f95/gr8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f283/12434208/305fad8242db/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f283/12434208/cf37e21af6b9/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f283/12434208/6809ca49217f/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f283/12434208/547cd9edce2a/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f283/12434208/120fbc766987/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f283/12434208/ed9f750c7f95/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f283/12434208/3a7ac778cee3/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f283/12434208/95d7a774e15c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f283/12434208/3d14022af9c6/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f283/12434208/305fad8242db/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f283/12434208/cf37e21af6b9/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f283/12434208/6809ca49217f/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f283/12434208/547cd9edce2a/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f283/12434208/120fbc766987/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f283/12434208/ed9f750c7f95/gr8.jpg

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Int J Biol Sci. 2024 Feb 25;20(5):1815-1832. doi: 10.7150/ijbs.85562. eCollection 2024.
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OTUD1 promotes hypertensive kidney fibrosis and injury by deubiquitinating CDK9 in renal epithelial cells.OTUD1通过去泛素化肾上皮细胞中的CDK9促进高血压性肾纤维化和损伤。
Acta Pharmacol Sin. 2024 Apr;45(4):765-776. doi: 10.1038/s41401-023-01192-6. Epub 2023 Dec 18.
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Roles of USP9X in cellular functions and tumorigenesis (Review).
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