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Cited by 18Wound Healing and TreatmentsDiabetic Foot Ulcer Assessment and ManagementTrace Elements in Health

Analyzing Immune Cell Infiltration and Copper Metabolism in Diabetic Foot Ulcers

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Yi, Wen-Juan, Yuan, Yifan, Bao, Qionglin, Zhao, Zhuowei, Ding, Hua-Sheng, Song, Jiquan·2024·Journal of Inflammation Research
DOI 10.2147/jir.s452609PMC PMC11107912
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Abstract

Background: Diabetes impairs wound healing, notably in diabetic foot ulcers (DFU). Stress, marked by the accumulation of lipoylated mitochondrial enzymes and the depletion of Fe-S cluster proteins, triggers cuproptosis-a distinct form of cell death. The involvement of copper in the pathophysiology of DFU has been recognized, and currently, a copper-based therapeutic strategy is emerging as a viable option for enhancing ulcer healing. This study investigates genes linked to copper metabolism in DFU, aiming to uncover potential targets for therapeutic intervention. Methods: Two diabetic wound Gene Expression Omnibus (GEO) datasets were analyzed to study immune cell dysregulation in diabetic wounds. Differentially expressed genes related to copper metabolism were identified and analyzed using machine learning methods. Gene ontology, pathway enrichment, and immune infiltration analyses were performed using DFU samples. The expression of identified genes was validated using qRT-PCR and single-cell RNA sequencing. Results: Ten genes associated with copper metabolism were identified. Among these, SLC31A1 and ADNP were found to be significantly differentially expressed in DFU. Notably, SLC31A1 exhibited higher expression in macrophages, whereas ADNP was found to be highly expressed in fibroblasts and chondrocytes. Conclusion: The study indicates a close link between copper metabolism, the infiltration of immune cells, and DFU. It proposes that copper metabolism could influence the progression of DFU through the activation of immune responses. These observations offer fresh perspectives on the underlying mechanisms of DFU and identify potential targets for therapeutic intervention.

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  • Insufficient local copper levels contribute to impaired healing in chronic wounds.

    “This study supports our hypothesis that less copper is delivered to chronic wounds, which impairs the key wound healing processes.”

    From The Journey of Copper-Impregnated Dressings in Wound Healing: From a Medical Hypothesis to Clinical Practice (2025) · cites this paper as [62]

    The Introduction reports lower serum copper in patients with diabetic foot ulcers and describes copper’s role in collagen crosslinking and angiogenesis. It does not establish that less copper is delivered to wounds locally or that a local deficiency causes impaired healing; the Discussion describes the link between copper metabolism and ulcers as suggestive. (LLM, conf=0.86)

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  • SLC31A1 is downregulated in refractory diabetic foot ulcers compared to healthy controls and acute wounds.

    “Yi et al. found that SLC31A1, a copper transporter, was significantly downregulated in refractory diabetic foot ulcers (DFUs) as compared to healthy controls and acute traumatic wounds [62].”

    From The Journey of Copper-Impregnated Dressings in Wound Healing: From a Medical Hypothesis to Clinical Practice (2025) · cites this paper as [62]

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Cited by

Sorted by citations

Authors
Yi, W.-J., Yuan, Y., Bao, Q., Zhao, Z., Ding, H.-S., & Song, J.
Affiliations
  • Sichuan University (CN)
  • Huazhong University of Science and Technology (CN)
  • Wuhan University (CN)
  • Southern Medical University Shenzhen Hospital (CN)
  • Zhongnan Hospital of Wuhan University (CN)
Corresponding author
Ding, Hua-Sheng
ORCID
Yuan, Yifan
Venue
Journal of Inflammation Research
Publisher
Informa UK Limited
Published
2024-05
Volume
Volume 17
Pages
3143-3157
ISSN
1178-7031 (ISSN-L)
DOI
10.2147/jir.s452609
PMC
PMC11107912
OpenAlex
W4397009009
Cited by
18
References
1
Citations by year
2026: 5 · 2025: 9 · 2024: 4
FWCI
2.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Inflammation Research (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
Topics
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetic Foot Ulcer Assessment and Management
  • Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Keywords
diabetic foot ulcer, copper metabolism, cuproptosis, immune cell infiltration, SLC31A1, ADNP, wound healing, macrophages, fibroblasts, chondrocytes, differentially expressed genes, therapeutic target

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