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Cited by 48Diabetic Foot Ulcer Assessment and ManagementWound Healing and TreatmentsCancer, Hypoxia, and Metabolism

Mechanism of damage of HIF-1 signaling in chronic diabetic foot ulcers and its related therapeutic perspectives

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Zhu, Dong, Wei, Wuhan, Zhang, Jingyu, Zhao, Bingkun, Li, Qiang, Jin, Peisheng·2024·Heliyon
DOI 10.1016/j.heliyon.2024.e24656PMC PMC10839564
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Abstract

Diabetic foot ulcer (DFU) is a chronic complication of diabetes. Wound healing in patients with DFU is generally very slow, with a high recurrence rate even after the ulcer healed. The DFU remains a major clinical challenge due to a lack of understanding of its pathogenesis. Given the significant impact of DFU on patient health and medical costs, enhancing our understanding of pathophysiological alterations and wound healing in DFU is critical. A growing body of research has shown that impaired activation of the HIF-1 pathway in diabetics, which weakens HIF-1 mediated responses to hypoxia and leads to down-regulation of its downstream target genes, leading to incurable diabetic foot ulcers. By analyzing and summarizing the literature in recent years, this review summarizes the mechanism of HIF-1 signaling pathway damage in the development of DFU, analyzes and compares the application of PHD inhibitors, VHL inhibitors, biomaterials and stem cell therapy in chronic wounds of diabetes, and proposes a new treatment scheme mediated by participation in the HIF-1 signaling pathway, which provides new ideas for the treatment of DFU.

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  • Chronic hyperglycaemia is associated with heightened ROS levels from mitochondrial and cytosolic compartments, enabling HIF-1α accumulation by interfering with PHD activity through oxygen-independent mechanisms.

    “Chronic hyperglycaemia is associated with is associated with heightened reactive oxygen species levels originating from mitochondrial and cytosolic compartment, which enables HIF-1α accumulation by interfering with prolyl hydroxylase activity through oxygen-independent mechanisms [[233], [234], [235]].”

    From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [234]

    In “Hyperglycemia promotes PHD-mediated degradation of HIF-1,” the paper says high glucose increases PHD-mediated HIF-1α degradation rather than allowing HIF-1α to accumulate by interfering with PHD. The “HIF-1 damage leads to downregulation of its target gene” section links mitochondrial ROS overproduction to PHD-dependent HIF-1 inhibition, not to ROS-driven HIF-1α accumulation. Page numbers are not provided in our copy. (LLM, conf=0.88)

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References 71 · Cited by 48

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Authors
Zhu, D., Wei, W., Zhang, J., Zhao, B., Li, Q., & Jin, P.
Affiliations
Affiliated Hospital of Xuzhou Medical College (CN)
Corresponding author
  • Zhao, Bingkun
  • Li, Qiang
  • Jin, Peisheng
ORCID
Venue
Heliyon
Publisher
Elsevier BV
Published
2024-02
Volume
10
Issue
3
Pages
e24656
ISSN
2405-8440 (ISSN-L)
DOI
10.1016/j.heliyon.2024.e24656
PMC
PMC10839564
OpenAlex
W4391188910
Cited by
48
References
71
Citations by year
2026: 22 · 2025: 20 · 2024: 6
FWCI
2.82
Type
journal article
Language
en
Open access
Licence
Locations
  • Heliyon (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (82172224)
  • Natural Science Foundation of Jiangsu Province (BK20201155)
  • Xuzhou Medical University (2022104922)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetic Foot Ulcer Assessment and Management
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords
diabetic foot ulcer, HIF-1 signaling, hypoxia, wound healing, chronic wounds, PHD inhibitors, biomaterials, stem cell therapy, diabetes complications

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