Evidence mapPaperPMID 40993725Full record

ArticleJournal of orthopaedic surgery and research2025

USP28 participates in high glucose-mediated endothelial dysfunction via deubiquitinating SIRT1 protein in diabetic foot ulcers.

Qiong Liu, Jin Zhang, Jichang Bai, Kuanzhi Liu

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Article in Journal of orthopaedic surgery and research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1 citing paper in PubMed.

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5 · Who and what money

Authors and funding

4 authors.

Qiong LiuDepartment of Endocrinology, The Second Hospital of Shijiazhuang, Shijiazhuang, China.
Jin ZhangDepartment of General Practitioner, The Second Hospital of Shijiazhuang, Shijiazhuang, China.
Jichang BaiDepartment of Endocrinology, The Second Hospital of Shijiazhuang, Shijiazhuang, China.
Kuanzhi LiuDepartment of Endocrinology, The Third Hospital of Hebei Medical University, No. 139, Ziqiang Road, Shijiazhuang, 050051, China. tsdxx19@126.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSilent information regulator sirtuin 1 (SIRT1) protects and improves diabetic wound healing, but SIRT1 undergoes ubiquitination degradation in various cellular environments. The research aims to reveal a mechanism related to SIRT1 deubiquitination to attenuate HG-induced injury in human umbilical vein endothelial cells (HUVECs).

methodsHUVECs treated with high glucose (HG) were utilized to simulate hyperglycemic conditions in vitro. Cell viability, proliferation, apoptosis, invasion, and angiogenesis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, 5-ethynyl-2'-deoxyuridine, flow cytometry, transwell, and tube formation assays, respectively. Ferroptosis was analyzed by analyzing Fe

resultsSerum SIRT1 mRNA levels were lower in patients with DFUs. SIRT1 overexpression impaired HG-induced injury, ERS, and ferroptosis in HUVECs. USP28 deubiquitinates and stabilizes SIRT1 protein. USP28 overexpression eased HG-induced injury, ERS, and ferroptosis in HUVECs, but the USP28 inhibitor AZ1 counteracted the function of USP28 overexpression. Furthermore, both SIRT1 knockdown and the SIRT1 inhibitor EX-527 undercut USP28 overexpression-mediated protective effect on HUVEC injury, ERS, and ferroptosis under HG stimulation. Additionally, USP28 regulated the NRF2/HO-1 pathway by deubiquitinating SIRT1 in HG-stimulated HUVECs.

conclusionUSP28 weakens HG-mediated endothelial dysfunction via activating the NRF2/HO-1 pathway through stabilizing SIRT1 protein, indicating that targeting USP28 is the direction for developing clinical strategies for diabetic wound healing.

Indexed as

Diabetic FootGlucoseSirtuin 1UbiquitinationUbiquitin ThiolesteraseApoptosisCells, CulturedEndoplasmic Reticulum Chaperone BiPEndoplasmic Reticulum StressHumansHuman Umbilical Vein Endothelial CellsMaleEndoplasmic Reticulum Chaperone BiPGlucoseHSPA5 protein, humanSIRT1 protein, humanSirtuin 1Ubiquitin ThiolesteraseDiabeticFerroptosisSIRT1USP28Wound healing

Identifiers

PMID40993725
PMCPMC12462188

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.