ArticleThe Journal of clinical investigation2016
PKCδ inhibition normalizes the wound-healing capacity of diabetic human fibroblasts.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 88 citations in OpenAlex.
- Advances in Chinese herbal medicine for diabetic wound treatment: from tradition to innovation.Chinese medicine · 2026Review
- Abnormally Elevated PKCδ Delays Diabetic Wound Healing by Inhibiting the GAD1-GABA Pathway.Diabetes & metabolism journal · 2026Article
- Topical Probiotics in Diabetic Wound Healing: Emerging Therapeutic Strategies.International journal of molecular sciences · 2026Review
- Unraveling the Mechanisms of Diabetic Wounds: Insights into Pathogenesis and Advanced Treatment Strategies.Current diabetes reviews · 2026Review
- Development and validation of a predictive model for cervical insufficiency incorporating AMH and androstenedione.Scientific reports · 2025Article
- Impact of 4-Environment & health (Washington, D.C.) · 2025Article
- Mechanisms and therapeutic opportunities in metabolic aberrations of diabetic wounds: a narrative review.Cell death & disease · 2025Review
- Revealing the molecular mechanisms in wound healing and the effects of different physiological factors including diabetes, age, and stress.Journal of molecular histology · 2024Review
- Unraveling the Enigma of Organismal Death: Insights, Implications, and Unexplored Frontiers.Physiology (Bethesda, Md.) · 2024Review
- Upregulation of rate-limiting enzymes in cholesterol metabolism by PKCδ mediates endothelial apoptosis in diabetic wound healing.Cell death discovery · 2024Article
- PKCμ promotes keratinocyte cell migration through Cx43 phosphorylation-mediated suppression of intercellular communication.iScience · 2024Article
- Topical Anti-ulcerogenic Effect of the Beta-adrenergic Blockers on Diabetic Foot Ulcers: Recent Advances and Future Prospectives.Current diabetes reviews · 2024Review
- Reduced methylation correlates with diabetic nephropathy risk in type 1 diabetes.The Journal of clinical investigation · 2023Article
- The Problem of Wound Healing in Diabetes-From Molecular Pathways to the Design of an Animal Model.International journal of molecular sciences · 2022Review
- Insulin's actions on vascular tissues: Physiological effects and pathophysiological contributions to vascular complications of diabetes.Molecular metabolism · 2021Review
- Verbascoside Protects Gingival Cells against High Glucose-Induced Oxidative Stress via PKC/HMGB1/RAGE/NFκB Pathway.Antioxidants (Basel, Switzerland) · 2021Article
- Article
- Cancer-associated fibroblasts promote the survival of irradiated nasopharyngeal carcinoma cells via the NF-κB pathway.Journal of experimental & clinical cancer research : CR · 2021Article
- The Role of Oxidative Stress and Antioxidants in Diabetic Wound Healing.Oxidative medicine and cellular longevity · 2021Review
- Novel Genes Potentially Involved in Fibroblasts of Diabetic Wound.Journal of diabetes research · 2021Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Abnormal fibroblast function underlies poor wound healing in patients with diabetes; however, the mechanisms that impair wound healing are poorly defined. Here, we evaluated fibroblasts from individuals who had type 1 diabetes (T1D) for 50 years or more (Medalists, n = 26) and from age-matched controls (n = 7). Compared with those from controls, Medalist fibroblasts demonstrated a reduced migration response to insulin, lower VEGF expression, and less phosphorylated AKT (p-AKT), but not p-ERK, activation. Medalist fibroblasts were also functionally less effective at wound closure in nude mice. Activation of the δ isoform of protein kinase C (PKCδ) was increased in postmortem fibroblasts from Medalists, fibroblasts from living T1D subjects, biopsies of active wounds of living T1D subjects, and granulation tissues from mice with streptozotocin-induced diabetes. Diabetes-induced PKCD mRNA expression was related to a 2-fold increase in the mRNA half-life. Pharmacologic inhibition and siRNA-mediated knockdown of PKCδ or expression of a dominant-negative isoform restored insulin signaling of p-AKT and VEGF expression in vitro and improved wound healing in vivo. Additionally, increasing PKCδ expression in control fibroblasts produced the same abnormalities as those seen in Medalist fibroblasts. Our results indicate that persistent PKCδ elevation in fibroblasts from diabetic patients inhibits insulin signaling and function to impair wound healing and suggest PKCδ inhibition as a potential therapy to improve wound healing in diabetic patients.
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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.