USP7-stabilised HIPK2 promotes high glucose-induced endothelial cell dysfunctions to accelerate diabetic foot ulcers.

IF 2.5 4区医学 Q3 ENDOCRINOLOGY & METABOLISM

Archives of Physiology and Biochemistry Pub Date : 2024-07-27 DOI:10.1080/13813455.2024.2376815

Huimin Huang, Yangyong Huang

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Abstract

Background: This study aimed to explore the molecular mechanism of homeodomain-interacting protein kinase 2 (HIPK2) in diabetic foot ulcers (DFU).

Methods: High glucose (HG)-induced human umbilical vein endothelial cells (HUVECs) were used to construct DFU cell models. Cell functions were determined using CCK8 assay, EdU assay, flow cytometry, transwell assay, wound healing assay and tube formation assay. Quantitative real-time PCR and western blot were applied to measure the gene expression.

Results: HG treatment suppressed HUVECs proliferation, invasion, migration, and angiogenesis, while enhanced apoptosis. HIPK2 was overexpressed in DFU patients, and its knockdown alleviated HG-induced HUVECs dysfunctions. USP7 stabilised HIPK2 protein by reducing its ubiquitination. USP7 overexpression promoted HG-induced HUVECs dysfunctions, and HIPK2 upregulation also reversed the regulation of USP7 knockdown on HG-induced HUVECs dysfunctions. USP7/HIPK2 axis inhibited the activity of PI3K/AKT pathway.

Conclusion: Our study revealed that USP7-stabilised HIPK2 contributed to HG-induced HUVECs dysfunctions, thus accelerating DFU process.

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USP7 稳定的 HIPK2 促进高血糖诱导的内皮细胞功能障碍，从而加速糖尿病足溃疡。

背景方法：使用高糖（HG）诱导的人脐静脉内皮细胞（HUVECs）构建 DFU 细胞模型。使用 CCK8 检测法、EdU 检测法、流式细胞术、Transwell 检测法、伤口愈合检测法和管形成检测法测定细胞功能。采用实时定量 PCR 和 Western 印迹检测基因表达：结果：HG 处理抑制了 HUVECs 的增殖、侵袭、迁移和血管生成，同时增强了其凋亡。HIPK2在DFU患者中过表达，敲除HIPK2可缓解HG诱导的HUVECs功能障碍。USP7 通过减少泛素化稳定了 HIPK2 蛋白。USP7 的过表达促进了 HG 诱导的 HUVECs 功能障碍，而 HIPK2 的上调也逆转了 USP7 敲除对 HG 诱导的 HUVECs 功能障碍的调节作用。USP7/HIPK2 轴抑制了 PI3K/AKT 通路的活性：我们的研究表明，USP7稳定的HIPK2有助于HG诱导的HUVECs功能障碍，从而加速DFU进程。

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

Archives of Physiology and Biochemistry ENDOCRINOLOGY & METABOLISM-PHYSIOLOGY

CiteScore

6.90

自引率

3.30%

发文量

期刊介绍： Archives of Physiology and Biochemistry: The Journal of Metabolic Diseases is an international peer-reviewed journal which has been relaunched to meet the increasing demand for integrated publication on molecular, biochemical and cellular aspects of metabolic diseases, as well as clinical and therapeutic strategies for their treatment. It publishes full-length original articles, rapid papers, reviews and mini-reviews on selected topics. It is the overall goal of the journal to disseminate novel approaches to an improved understanding of major metabolic disorders. The scope encompasses all topics related to the molecular and cellular pathophysiology of metabolic diseases like obesity, type 2 diabetes and the metabolic syndrome, and their associated complications. Clinical studies are considered as an integral part of the Journal and should be related to one of the following topics: -Dysregulation of hormone receptors and signal transduction -Contribution of gene variants and gene regulatory processes -Impairment of intermediary metabolism at the cellular level -Secretion and metabolism of peptides and other factors that mediate cellular crosstalk -Therapeutic strategies for managing metabolic diseases Special issues dedicated to topics in the field will be published regularly.