ArticleWound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society2016
Integrative analysis of miRNA and mRNA paired expression profiling of primary fibroblast derived from diabetic foot ulcers reveals multiple impaired cellular functions.
Article in Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 92 citations in OpenAlex.
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- Half-Life as a Therapeutic Design Axis: Targeting Short-Lived lncRNAs With Antisense Oligonucleotides.IUBMB life · 2026Review
- Single-cell RNA sequencing in diabetic foot ulcers: pathogenesis, biomarkers, and translational potential.Frontiers in clinical diabetes and healthcare · 2026Review
- Revolutionizing Diabetic Foot Ulcer Management: Exploring the Therapeutic Potential of Natural Products.Current pharmaceutical design · 2026Review
- Improved wound healing by dual inhibition of miR-146a-5p and miR-29a-3p supports a network action of dysregulated miRNAs in diabetic skin.Diabetologia · 2026Article
- Enhanced Ciliogenesis of Human Bronchial Epithelial Cells by Simulated Microgravity.Life (Basel, Switzerland) · 2025Article
- Emerging Biomarkers and Nanobiosensing Strategies in Diabetes.Biosensors · 2025Review
- MicroRNA profiles of four induced pluripotent stem cell lines derived from distinct tissues.BMC research notes · 2025Article
- The development of a direct co-culture-based model for diabetic foot ulcer mimicking inflammation and impaired phagocytosis.In vitro models · 2025Article
- Targeting diabetic foot ulcer pathophysiology: altered signaling pathways and 3D scaffold as an emerging treatment strategy.3 Biotech · 2025Review
- Diabetic Foot Ulcers: Pathophysiology, Immune Dysregulation, and Emerging Therapeutic Strategies.Biomedicines · 2025Review
- MicroRNA miR-145-5p Inhibits Cutaneous Wound Healing by Targeting PDGFD in Diabetic Foot Ulcer.Biochemical genetics · 2024Article
- Molecular Morbidity Score-Can MicroRNAs Assess the Burden of Disease?International journal of molecular sciences · 2024Review
- Functionalised biomaterials as synthetic extracellular matrices to promote vascularisation and healing of diabetic wounds.Cell and tissue research · 2024Review
- Improving Cutaneous Wound Healing in Diabetic Mice Using Naturally Derived Tissue-Engineered Biological Dressings Produced under Serum-Free Conditions.Stem cells international · 2024Article
- Identification of hub genes and pathways associated with cellular senescence in diabetic foot ulcers via comprehensive transcriptome analysis.Journal of cellular and molecular medicine · 2024Article
- The Potential of miR-21 in Stem Cell Differentiation and its Application in Tissue Engineering and Regenerative Medicine.Stem cell reviews and reports · 2023Review
- Therapeutic role of growth factors in treating diabetic wound.World journal of diabetes · 2023Review
- Molecular Pathophysiology of Chronic Wounds: Current State and Future Directions.Cold Spring Harbor perspectives in biology · 2023Review
- Calreticulin: a multifunctional protein with potential therapeutic applications for chronic wounds.Frontiers in medicine · 2023Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Diabetic foot ulcers (DFUs) are one of the major complications of diabetes. Its molecular pathology remains poorly understood, impeding the development of effective treatments. Although it has been established that multiple cell types, including fibroblasts, keratinocytes, macrophages, and endothelial cells, all contribute to inhibition of healing, less is known regarding contributions of individual cell type. Thus, we generated primary fibroblasts from nonhealing DFUs and evaluated their cellular and molecular properties in comparison to nondiabetic foot fibroblasts (NFFs). Specifically, we analyzed both micro-RNA and mRNA expression profiles of primary DFU fibroblasts. Paired genomic analyses identified a total of 331 reciprocal miRNA-mRNA pairs including 21 miRNAs (FC > 2.0) along with 239 predicted target genes (FC > 1.5) that are significantly and differentially expressed. Of these, we focused on three miRNAs (miR-21-5p, miR-34a-5p, miR-145-5p) that were induced in DFU fibroblasts as most differentially regulated. The involvement of these microRNAs in wound healing was investigated by testing the expression of their downstream targets as well as by quantifying cellular behaviors in prospectively collected and generated cell lines from 15 patients (seven DFUF and eight NFF samples). We found large number of downstream targets of miR-21-5p, miR-34a-5p, miR-145-5p to be coordinately regulated in mRNA profiles, which was confirmed by quantitative real-time PCR. Pathway analysis on paired miRNA-mRNA profiles predicted inhibition of cell movement and cell proliferation, as well as activation of cell differentiation and senescence in DFU fibroblasts, which was confirmed by cellular assays. We concluded that induction of miR-21-5p, miR-34a-5p, miR-145-5p in DFU dermal fibroblasts plays an important role in impairing multiple cellular functions, thus contributing to overall inhibition of healing in DFUs.
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Registered trials
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.