ArticlePloS one2014
High-glucose inhibits human fibroblast cell migration in wound healing via repression of bFGF-regulating JNK phosphorylation.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 159 citations in OpenAlex.
- Endothelial-Fibroblast Organoids Generated in Hydrogel Microchamber Arrays: A Translational Model of Vascular Dysfunction in Cardio-Kidney-Metabolic Disease.Journal of vascular research · 2026Article
- Semaglutide and Liraglutide Modulate Oxidative Stress and Wound Repair in Normal Human Skin Cells Exposed to an In Vitro Diabetic-like Environment.International journal of molecular sciences · 2026Article
- Enzymatically triggered glucose-releasing scaffolds as nutritional supports for millimeter-scale tissue engineering.Materials today. Bio · 2026Article
- In Vitro Evaluation of Novel Synthetic Benzimidazolium-Chalcone Hybrids: Antioxidant and Regenerative Effects in Diabetic Wound Healing.Applied biochemistry and biotechnology · 2026Article
- Collagen promotes PD-L1 overexpression in fibroblasts through binding to CD44 and activating YAP1 signaling during keloid formation.Scientific reports · 2026Article
- Baicalin-loaded chitosan hydrogel accelerates diabetic foot ulcer healing by regulating MAPK1 expression.Journal of molecular histology · 2026Article
- aFGF rescues high glucose-induced senescent fibroblasts and improves diabetic wound healing by regulating SIRT1/STAT3 pathway.Scientific reports · 2026Article
- The Interplay Between Stiffness and Hyperglycemia on Diabetic Foot Ulcer Wound Closure.Cellular and molecular bioengineering · 2026Article
- Targeting Oxidative Stress and Apoptosis via PI3K/Akt/Nrf2 Pathway: The Therapeutic Role ofJournal of diabetes research · 2026Article
- A Novel Murine Model for Studying Impaired Wound Healing in Diabetes.International wound journal · 2026Article
- Fibroblast Dysfunction and Immune Dysregulation Impair Palatal Wound Healing in Diabetic Rats.International dental journal · 2025Article
- Sinapic acid accelerates diabetic wound healing by promoting angiogenesis and reducing oxidative stress.Scientific reports · 2025Article
- From Diet to Scar: Novel Mendelian Randomization and Mediation Analyses Linking Dietary Habits, Gut Microbiota, and Hypertrophic Scarring.Food science & nutrition · 2025Article
- Mitochondrial aldehyde dehydrogenase restores the migratory capacity inhibited by high glucose-induced hyperosmolality.Scientific reports · 2025Article
- Mechanisms and therapeutic opportunities in metabolic aberrations of diabetic wounds: a narrative review.Cell death & disease · 2025Review
- Methylglyoxal impairs human dermal fibroblast survival and migration by alteringToxicology reports · 2024Article
- Anti-Inflammatory and Wound Healing Properties of Different Honey Varieties from Romania and Correlations to Their Composition.Life (Basel, Switzerland) · 2024Article
- Fibroblast growth factor 2 promotes osteo/odontogenic differentiation in stem cells from the apical papilla by inhibiting PI3K/AKT pathway.Scientific reports · 2024Article
- Engineered exosomes as a prospective therapy for diabetic foot ulcers.Burns & trauma · 2024Review
- An evaluation of photobiomodulation effects on human gingival fibroblast cells under hyperglycemic condition: an in vitro study.Lasers in medical science · 2023Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One of the major symptoms of diabetes mellitus (DM) is delayed wound healing, which affects large populations of patients worldwide. However, the underlying mechanism behind this illness remains elusive. Skin wound healing requires a series of coordinated processes, including fibroblast cell proliferation and migration. Here, we simulate DM by application of high glucose (HG) in human foreskin primary fibroblast cells to analyze the molecular mechanism of DM effects on wound healing. The results indicate that HG, at a concentration of 30 mM, delay cell migration, but not cell proliferation. bFGF is known to promote cell migration that partially rescues HG effects on cell migration. Molecular and cell biology studies demonstrated that HG enhanced ROS production and repressed JNK phosphorylation, but did not affect Rac1 activity. JNK and Rac1 activation were known to be important for bFGF regulated cell migration. To further confirm DM effects on skin repair, a type 1 diabetic rat model was established, and we observed the efficacy of bFGF on both normal and diabetic rat skin repair. Furthermore, proteomic studies identified an increase of Annexin A2 protein nitration in HG-stressed fibroblasts and the nitration was protected by activation of bFGF signaling. Treatment with FGFR1 and JNK inhibitors delayed cell migration and increased Annexin A2 nitration levels, indicating that Annexin A2 nitration is modulated by bFGF signaling via activation of JNK. Together with these results, our data suggests that the HG-mediated delay of cell migration is linked to the inhibition of bFGF signaling, specifically through JNK suppression.
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