ArticleJournal of orthopaedic surgery and research2023
Adipose-derived stem cell exosome NFIC improves diabetic foot ulcers by regulating miR-204-3p/HIPK2.
Article in Journal of orthopaedic surgery and research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- miR-191-5p inhibits angiogenesis in diabetic foot ulcers wound healing via regulating VEGFA.European journal of medical research · 2025Article
- Hypoxic adipose-derived stem cell exosomes as carriers of miR-100-5p to enhance angiogenesis and suppress inflammation in diabetic foot ulcers.Journal of cell communication and signaling · 2025Article
- MicroRNA-4516 in extracellular vesicles-derived mesenchymal stem cells suppressed integrin αV-mediated lung fibrosis.Stem cell research & therapy · 2025Article
- Exo-hydrogel therapy: a revolutionary approach to managing diabetic complications.Journal of nanobiotechnology · 2025Review
- Cell migration in diabetic wound healing: Molecular mechanisms and therapeutic strategies (Review).International journal of molecular medicine · 2025Review
- Porcine pericardial decellularized matrix bilayer patch containing adipose stem cell-derived exosomes for the treatment of diabetic wounds.Materials today. Bio · 2025Article
- The therapeutic effect of exosomes in type 2 diabetes mellitus and its complications.Frontiers in medicine · 2025Review
- Mesenchymal Stem Cell-Derived Exosomes Hold Promise in the Treatment of Diabetic Foot Ulcers.International journal of nanomedicine · 2025Review
- Advances in the Role of Stem Cell-Derived Exosomes in Diabetic Foot Wound Healing.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Review
- Recent Progress in Mesenchymal Stem Cell-Derived Exosomes for Skin Wound Repair.Cell biochemistry and biophysics · 2024Review
- Exosomes: compositions, biogenesis, and mechanisms in diabetic wound healing.Journal of nanobiotechnology · 2024Review
- Adipose-derived stem cells in diabetic foot care: Bridging clinical trials and practical application.World journal of diabetes · 2024Review
- Adipose-Derived Stem Cell Exosomes Facilitate Diabetic Wound Healing: Mechanisms and Potential Applications.International journal of nanomedicine · 2024Review
- Stem Cell-Derived Extracellular Vesicles: Promising Therapeutic Opportunities for Diabetic Wound Healing.International journal of nanomedicine · 2024Review
- The emerging modulators of non-coding RNAs in diabetic wound healing.Frontiers in endocrinology · 2024Review
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDiabetic foot ulcers (DFU) are a serious complication of diabetes that lead to significant morbidity and mortality. Recent studies reported that exosomes secreted by human adipose tissue-derived mesenchymal stem cells (ADSCs) might alleviate DFU development. However, the molecular mechanism of ADSCs-derived exosomes in DFU is far from being addressed.
methodsHuman umbilical vein endothelial cells (HUVECs) were induced by high-glucose (HG), which were treated with exosomes derived from nuclear factor I/C (NFIC)-modified ADSCs. MicroRNA-204-3p (miR-204-3p), homeodomain-interacting protein kinase 2 (HIPK2), and NFIC were determined using real-time quantitative polymerase chain reaction. Cell proliferation, apoptosis, migration, and angiogenesis were assessed using cell counting kit-8, 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, wound healing, and tube formation assays. Binding between miR-204-3p and NFIC or HIPK2 was predicted using bioinformatics tools and validated using a dual-luciferase reporter assay. HIPK2, NFIC, CD81, and CD63 protein levels were measured using western blot. Exosomes were identified by a transmission electron microscope and nanoparticle tracking analysis.
resultsmiR-204-3p and NFIC were reduced, and HIPK2 was enhanced in DFU patients and HG-treated HUVECs. miR-204-3p overexpression might abolish HG-mediated HUVEC proliferation, apoptosis, migration, and angiogenesis in vitro. Furthermore, HIPK2 acted as a target of miR-204-3p. Meanwhile, NFIC was an upstream transcription factor that might bind to the miR-204-3p promoter and improve its expression. NFIC-exosome from ADSCs might regulate HG-triggered HUVEC injury through miR-204-3p-dependent inhibition of HIPK2.
conclusionExosomal NFIC silencing-loaded ADSC sheet modulates miR-204-3p/HIPK2 axis to suppress HG-induced HUVEC proliferation, migration, and angiogenesis, providing a stem cell-based treatment strategy for DFU.
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