去泛素化酶 USP4 通过稳定 RYBP 促进滋养层功能障碍

IF 1.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xuandi Wu, Jia Hong, Liang Hong
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引用次数: 0

摘要

以往的研究表明,螺旋动脉重塑受损、胎盘功能障碍和滋养细胞浸润不足是子痫前期(PE)的病因和发病机制。据报道,环 1 和 YY1 结合蛋白(RYBP)与滋养细胞功能障碍有关。然而,RYBP参与滋养层细胞在PE发病机制中的分子机制尚不明确。采用实时定量聚合酶链反应(RT-qPCR)测定了RYBP和泛素特异性肽酶4(USP4)的mRNA水平。采用 Western 印迹法测定 RYBP、USP4、p-PI3K、PI3K、p-AKT 和 AKT 蛋白水平。使用 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-溴化四氮唑(MTT)、5-乙炔基-2'-脱氧尿苷(EdU)、流式细胞术、透孔法和伤口愈合法评估细胞活力、增殖、凋亡、侵袭和迁移。经过 ubibrowser 数据库分析,USP4 和 RYBP 之间的相互作用通过共免疫沉淀(CoIP)试验得到了验证。在 PE 患者的胎盘组织中,RYBP 和 USP4 表达上调。通过使用 JEG-3 和 HTR-8/SVneo 滋养层细胞,RYBP 过表达或 USP4 上调可阻碍细胞活力、增殖、侵袭、迁移并促进细胞凋亡。从机制上讲,USP4 可触发 RYBP 的去泛素化并阻止其降解。此外,USP4 还能通过调节 RYBP 来抑制 PI3K/AKT 信号通路。总之,USP4 介导的泛素化减少会通过增强 RYBP 的表达而对滋养细胞的功能产生不利影响,从而为 PE 提供了一个新的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Deubiquitinating Enzyme USP4 Promotes Trophoblast Dysfunction by Stabilizing RYBP.

Previous studies have suggested that impaired spiral artery remodeling, placental dysfunction, and insufficient trophoblast infiltration are the etiology and pathogenesis of Preeclampsia (PE). Ring 1 and YY1 binding protein (RYBP) has been reported to be associated with trophoblast dysfunction. However, the molecular mechanism of RYBP involved in trophoblasts in the pathogenesis of PE is poorly defined. RYBP and Ubiquitin-specific peptidase 4 (USP4) mRNA levels were determined using real-time quantitative polymerase chain reaction (RT-qPCR). RYBP, USP4, p-PI3K, PI3K, p-AKT, and AKT protein levels were measured using western blot assay. Cell viability, proliferation, apoptosis, invasion, and migration were assessed using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, and wound healing assays. After ubibrowser database analysis, the interaction between USP4 and RYBP was verified using Co-immunoprecipitation (CoIP) assay. RYBP and USP4 expression were upregulated in placental tissues from PE patients. By using JEG-3 and HTR-8/SVneo trophoblast cells, RYBP overexpression or USP4 upregulation could hinder cell viability, proliferation, invasion, migration, and promote apoptosis. Mechanistically, USP4 could trigger the deubiquitination of RYBP and prevent its degradation. In addition, USP4 repressed the PI3K/AKT signaling pathway by regulating RYBP. In total, Decreased USP4-mediated ubiquitination results in an adverse impact on trophoblast function by enhancing RYBP expression, providing a novel therapeutic target for PE.

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来源期刊
Cell Biochemistry and Biophysics
Cell Biochemistry and Biophysics 生物-生化与分子生物学
CiteScore
4.40
自引率
0.00%
发文量
72
审稿时长
7.5 months
期刊介绍: Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized. Examples of subject areas that CBB publishes are: · biochemical and biophysical aspects of cell structure and function; · interactions of cells and their molecular/macromolecular constituents; · innovative developments in genetic and biomolecular engineering; · computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies; · photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.
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