Evidence map›Paper›PMID 40394598›Full record

ArticleJournal of orthopaedic surgery and research2025

Exploring the mechanism by which UCHL3 alleviates diabetic foot ulcers: FOXM1/NLRP3 inflammasome-mediated angiogenesis and endothelial cell pyroptosis.

Xincheng Liao, Zhengying Jiang, Zhonghua Fu, Guanghua Guo

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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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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Xincheng LiaoMedical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, 330006, China.
Zhengying JiangMedical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, 330006, China.
Zhonghua FuMedical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, 330006, China.
Guanghua GuoMedical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, 330006, China. gggg2024@126.com.

Funding

National Natural Science Foundation of China Grant No. 82160380
6 · The paper itself

Abstract

backgroundThis study investigated the role of ubiquitin C-terminal hydrolase L3 (UCHL3) in regulating endothelial cell (EC) pyroptosis and angiogenesis in diabetic foot ulcers (DFUs), with a focus on FOXM1 and NLRP3 inflammasomes.

methodsDifferentially expressed genes in DFUs were identified using the GSE134431 dataset and cross-referenced with vascular formation-related factors from GeneCard and deubiquitinases from the UbiNet 2.0 database. A rat DFU model was used to evaluate wound healing, with or without UCHL3 overexpression and FOXM1 knockdown. Histological analysis and immunohistochemistry were employed to assess tissue morphology and the expression of CD31, eNOS, UCHL3, and FOXM1. In vitro, high glucose-induced human umbilical vein ECs (HUVECs) were transfected with UCHL3 overexpression and FOXM1 knockdown constructs. Cell viability, migration, and angiogenesis were assessed.

resultsUCHL3 expression was significantly reduced in DFU tissues. UCHL3 overexpression promoted wound healing in a rat model, while FOXM1 knockdown impaired wound healing and vascular formation. In HUVECs, UCHL3 overexpression enhanced cell viability, migration, and angiogenesis, accompanied by reduced NLRP3 and N-GSDMD levels. FOXM1 knockdown reversed these effects, but treatment with the NLRP3 inhibitor, MCC950, alleviated this damage.

conclusionUCHL3 enhances FOXM1 deubiquitination, inhibits NLRP3 inflammasome activation, and reduces EC pyroptosis, thereby contributing to DFU healing. UCHL3 and FOXM1 are potential therapeutic targets for DFU.

Indexed as

Diabetic FootEndothelial CellsForkhead Box Protein M1InflammasomesNeovascularization, PhysiologicNLR Family, Pyrin Domain-Containing 3 ProteinPyroptosisUbiquitin ThiolesteraseAngiogenesisAnimalsHumansHuman Umbilical Vein Endothelial CellsMaleRatsRats, Sprague-DawleyWound HealingForkhead Box Protein M1FOXM1 protein, humanInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanNlrp3 protein, ratUbiquitin ThiolesteraseDiabetic foot ulcersEndothelial cellsFOXM1NLRP3 inflammasomeUCHL3

Identifiers

PMID40394598
PMCPMC12090482

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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 OpenQuestion graph.