ArticleDiabetes2016
Restoration of Nrf2 Signaling Normalizes the Regenerative Niche.
Article in Diabetes, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Systematic review and meta-analysis of mouse models of diabetes-associated ulcers.BMJ open diabetes research & care · 2020Pooled it
- Mechanical, Redox, and Bioelectrical Coupling in Hydrogels for Cutaneous Regeneration: Network Design and Structure-Property Relationships.Gels (Basel, Switzerland) · 2026Review
- ROS-responsive microneedle patch delivering NMN@Cu/CeO₂ nanozyme for restoring immune microenvironment and mitochondrial homeostasis to potentiate diabetic wound healing.Journal of nanobiotechnology · 2026Article
- Nutritional Interventions to Optimize Orthobiologic Therapy Quality in Type 2 Diabetes Mellitus: Molecular Mechanisms and Clinical Framework: A Narrative Review.International journal of molecular sciences · 2026Review
- Unraveling the Mechanisms of Diabetic Wounds: Insights into Pathogenesis and Advanced Treatment Strategies.Current diabetes reviews · 2026Review
- Chinese traditional medicine complex hemorrhoidal analgesic cream promotes wound healing in diabetic rats after anal fistula surgery via Keap1/Nrf2 signaling pathway.Biochemistry and biophysics reports · 2025Article
- Reactive oxygen species counteract zebrafish wound contraction and promote wound healing.Biophysical journal · 2025Article
- Diabetic neuropathy: A NRF2 disease?Journal of diabetes · 2024Review
- Turmeric-Derived Nanoparticles Functionalized Aerogel Regulates Multicellular Networks to Promote Diabetic Wound Healing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The role of SLC7A11 in diabetic wound healing: novel insights and new therapeutic strategies.Frontiers in immunology · 2024Review
- Promising Phytoconstituents in Diabetes-related Wounds: Mechanistic Insights and Implications.Current diabetes reviews · 2024Review
- Functional nucleic acids for the treatment of diabetic complications.Nanoscale advances · 2023Review
- Milk-derived exosomes carrying siRNA-KEAP1 promote diabetic wound healing by improving oxidative stress.Drug delivery and translational research · 2023Article
- Pterostilbene attenuates hemin-induced dysregulation of macrophage M2 polarization via Nrf2 activation in experimental hyperglycemia.Inflammopharmacology · 2023Article
- Mechanisms of Nrf2 and NF-κB pathways in diabetic wound and potential treatment strategies.Molecular biology reports · 2023Review
- Antioxidant Activities of Natural Compounds from Caribbean Plants to Enhance Diabetic Wound Healing.Antioxidants (Basel, Switzerland) · 2023Review
- Monitoring Nrf2/ARE Pathway Activity with a New Zebrafish Reporter System.International journal of molecular sciences · 2023Article
- Antioxidant, Wound Healing Potential and In Silico Assessment of Naringin, Eicosane and Octacosane.Molecules (Basel, Switzerland) · 2023Article
- Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy.Frontiers in endocrinology · 2023Article
- Multifaceted roles of mitochondria in wound healing and chronic wound pathogenesis.Frontiers in cell and developmental biology · 2023Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Chronic hyperglycemia impairs intracellular redox homeostasis and contributes to impaired diabetic tissue regeneration. The Keap1/Nrf2 pathway is a critical regulator of the endogenous antioxidant response system, and its dysfunction has been implicated in numerous pathologies. Here we characterize the effect of chronic hyperglycemia on Nrf2 signaling within a diabetic cutaneous regeneration model. We characterized the effects of chronic hyperglycemia on the Keap1/Nrf2 pathway within models of diabetic cutaneous wound regeneration. We assessed reactive oxygen species (ROS) production and antioxidant gene expression following alterations in the Nrf2 suppressor Keap1 and the subsequent changes in Nrf2 signaling. We also developed a topical small interfering RNA (siRNA)-based therapy to restore redox homeostasis within diabetic wounds. Western blotting demonstrated that chronic hyperglycemia-associated oxidative stress inhibits nuclear translocation of Nrf2 and impairs activation of antioxidant genes, thus contributing to ROS accumulation. Keap1 inhibition increased Nrf2 nuclear translocation, increased antioxidant gene expression, and reduced ROS production to normoglycemic levels, both in vitro and in vivo. Topical siKeap1 therapy resulted in improved regenerative capacity of diabetic wounds and accelerated closure. We report that chronic hyperglycemia weakens the endogenous antioxidant response, and the consequences of this defect are manifested by intracellular redox dysregulation, which can be restored by Keap1 inhibition. Targeted siRNA-based therapy represents a novel, efficacious strategy to reestablish redox homeostasis and accelerate diabetic cutaneous tissue regeneration.
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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.