ArticlePLoS genetics2016
A Glutathione-Nrf2-Thioredoxin Cross-Talk Ensures Keratinocyte Survival and Efficient Wound Repair.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- The molecular mechanism of ferroptosis and its role in COPD.Frontiers in medicine · 2022Pooled it
- Bilirubin and the Yellow Players in Ferroptosis: A Delicate Balance in Human Health and Disease, with a Focus on the Liver, Cardiovascular System, and Brain.Biomolecules · 2026Review
- Disulfiram's Anti-Inflammatory and Antibacterial Effects in Fixed-Dose Combination Therapy for Scabies.Pharmaceutics · 2026Article
- Wound Healing Potential of Selenium and Nanoselenium.Biological trace element research · 2026Review
- Article
- Metabolite profiling of saliva for the discrimination of Behcet's disease, Sjögren's syndrome, and recurrent aphthous stomatitis.PloS one · 2026Article
- Light up the mitochondria: Smart tungstate-oligosaccharide nanoplatform orchestrates mitochondrial transfer from M2 macrophages to restore endothelial function for adaptive diabetic wound regeneration.Materials today. Bio · 2025Article
- The Role of Oxidative Stress in Skin Disorders Associated with Alcohol Dependency and Antioxidant Therapies.Molecules (Basel, Switzerland) · 2025Review
- The prostacyclin receptor PTGIR is a NRF2-dependent regulator of CD8Nature immunology · 2025Article
- Thirty years of NRF2: advances and therapeutic challenges.Nature reviews. Drug discovery · 2025Review
- Nonessential amino acid is not nonessential in geriatric patients: implications for maxillofacial wound healing and bone repair.Maxillofacial plastic and reconstructive surgery · 2025Review
- Mechanism of dracorhodin in accelerating diabetic foot ulcer healing via the Nrf2 pathway, a network pharmacology, molecular docking and experimental validation.Scientific reports · 2025Article
- Iron(ing) out parkinsonisms: The interplay of proteinopathy and ferroptosis in Parkinson's disease and tau-related parkinsonisms.Redox biology · 2025Review
- Apoptosis and Cell Clearance in Skin Wound Healing.Advances in experimental medicine and biology · 2025Review
- Dose-dependent effects of Nrf2 on the epidermis in chronic skin inflammation.Disease models & mechanisms · 2025Article
- Linking homocysteine and ferroptosis in cardiovascular disease: insights and implications.Apoptosis : an international journal on programmed cell death · 2024Review
- Ferroptosis crosstalk in anti-tumor immunotherapy: molecular mechanisms, tumor microenvironment, application prospects.Apoptosis : an international journal on programmed cell death · 2024Review
- Protocatechuic acid relieves ferroptosis in hepatic lipotoxicity and steatosis via regulating NRF2 signaling pathway.Cell biology and toxicology · 2024Article
- CircRNA_SLC8A1 alleviates hypertrophic scar progression by mediating the Nrf2-ARE pathway.Molecular biology reports · 2024Article
- Selenomethionine and Allicin Synergistically Mitigate Intestinal Oxidative Injury by Activating the Nrf2 Pathway.Toxics · 2024Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tripeptide glutathione is the most abundant cellular antioxidant with high medical relevance, and it is also required as a co-factor for various enzymes involved in the detoxification of reactive oxygen species and toxic compounds. However, its cell-type specific functions and its interaction with other cytoprotective molecules are largely unknown. Using a combination of mouse genetics, functional cell biology and pharmacology, we unraveled the function of glutathione in keratinocytes and its cross-talk with other antioxidant defense systems. Mice with keratinocyte-specific deficiency in glutamate cysteine ligase, which catalyzes the rate-limiting step in glutathione biosynthesis, showed a strong reduction in keratinocyte viability in vitro and in the skin in vivo. The cells died predominantly by apoptosis, but also showed features of ferroptosis and necroptosis. The increased cell death was associated with increased levels of reactive oxygen and nitrogen species, which caused DNA and mitochondrial damage. However, epidermal architecture, and even healing of excisional skin wounds were only mildly affected in the mutant mice. The cytoprotective transcription factor Nrf2 was strongly activated in glutathione-deficient keratinocytes, but additional loss of Nrf2 did not aggravate the phenotype, demonstrating that the cytoprotective effect of Nrf2 is glutathione dependent. However, we show that deficiency in glutathione biosynthesis is efficiently compensated in keratinocytes by the cysteine/cystine and thioredoxin systems. Therefore, our study highlights a remarkable antioxidant capacity of the epidermis that ensures skin integrity and efficient wound healing.
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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.