ArticleRedox biology2021
Protease-activated receptor 2 induces ROS-mediated inflammation through Akt-mediated NF-κB and FoxO6 modulation during skin photoaging.
Article in Redox biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 176 citations in OpenAlex.
- Protective effects of Oroxylum indicum seed extract against ultraviolet-induced skin photodamage through inhibition of STING and NF-κB signaling pathways.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2026Article
- BGP-15 ameliorates sepsis-induced cardiomyopathy via SIRT3/SOD2-associated antioxidant signaling and suppression of myocardial inflammation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Pseudorabies virus pUL40 drives inflammatory signaling through competitive hijacking of EphA2 from the Akt-EphA2 interaction.Veterinary research · 2026Article
- Hydroxytyrosol Improves UV-Induced Skin Photoaging via PI3K-AKT/MAPK/JAK-STAT and NF-κB Pathways: Insights From Keratinocytes and In Vivo Validation.Phytotherapy research : PTR · 2026Article
- From Waste to Beauty: Agri-Food By-Products as Sources of Antioxidant Compounds for Cosmeceutical Applications.Antioxidants (Basel, Switzerland) · 2026Review
- Luteolin fromPharmaceuticals (Basel, Switzerland) · 2026Article
- Advances in skin aging: integrating epigenetic, cellular, and immune mechanisms for targeted therapy.Immunity & ageing : I & A · 2026Review
- A multifunctional nano-hydrogel attenuates skin photoaging via regulating ECM microenvironment homeostasis.Materials today. Bio · 2026Article
- Chitosan-based nanozyme hydrogels: Advanced antioxidant and sustained-release systems for the prevention and treatment of skin photoaging.International journal of pharmaceutics: X · 2026Review
- Chrysanthemum indicum L.-derived extracellular vesicles enhance the therapeutic efficacy of cyclosporine a against dry eye disease.Journal of nanobiotechnology · 2026Article
- Diallyl disulfide reduces oxidative stress to mitigate uranium tailings radiation-induced damage to the hematopoietic system.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2026Article
- Exercise modulates redox homeostasis in cardiovascular and metabolic diseases: from bench to clinic.Cardiovascular diabetology · 2026Review
- Protease-activated receptors act as a liaison between metabolism and inflammation.Inflammopharmacology · 2026Review
- Dermal Fibroblast Senescence: The Central Hub of Skin Aging-From Intrinsic Dysfunction to Microenvironmental Remodeling.International journal of molecular sciences · 2026Review
- Epicatechin Gallate Ameliorates UVB-Induced Photoaging by Inhibiting p38α-Mediated Autophagy and Oxidative Stress.Antioxidants (Basel, Switzerland) · 2026Article
- Anti-Photoaging Effect of Soluble Microneedles Loaded with Hydroxytyrosol.International journal of molecular sciences · 2026Article
- Neferine alleviated corticosterone-induced depressive-like behaviors in mice via the inhibition of TNF/NF-κB pathway by binding to PPARγ.Molecular neurobiology · 2026Article
- Design and Factorial Optimization of Curcumin and Resveratrol Co-Loaded Lipid Nanocarriers for Topical Delivery.Pharmaceutics · 2026Article
- Ginsenoside Re Ameliorates UVB-Induced Skin Photodamage by Modulating the Glutathione Metabolism Pathway: Insights from Integrated Transcriptomic and Metabolomic Analyses.International journal of molecular sciences · 2026Article
- Targeting the nuclear factor kappa B pathway for the medical management of intervertebral disc degeneration.Frontiers in neuroscience · 2026Review
43 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
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Long-term exposure to ultraviolet irradiation to skin leads to deleterious intracellular effects, including reactive oxygen species (ROS) production and inflammatory responses, causing accelerated skin aging. Previous studies have demonstrated that increased expression and activation of protease-activated receptor 2 (PAR2) and Akt is observed in keratinocyte proliferation, suggesting their potential regulatory role in skin photoaging. However, the specific underlying molecular mechanism of PAR2 and the Akt/NF-κB/FoxO6-mediated signaling pathway is not clearly defined. In this study, we first used the UVB-irradiated photoaged skin of hairless mice and observed an increase in PAR2 and Gαq expression and PI3-kinase/Akt, NF-κB, and suppressed FoxO6. Consequently, increased levels of proinflammatory cytokines and decreased levels of antioxidant MnSOD was observed. Next, to investigate PAR2-specific roles in inflammation and oxidative stress, we used photoaged hairless mice topically applied with PAR2 antagonist GB83 and photoaged PAR2 knockout mice. PAR2 inhibition and deletion significantly suppressed inflammatory and oxidative stress levels, which were associated with decreased IL-6 and IL-1β levels and increased MnSOD levels, respectively. Furthermore, NF-κB phosphorylation and decreased FoxO6 was reduced by PAR2 inhibition and deletion in vivo. To confirm the in vivo results, we conducted PAR2 knockdown and overexpression in UVB-irradiated HaCaT cells. In PAR2 knockdown cells by si-PAR2 treatment, it suppressed Akt/NF-κB and increased FoxO6, whereas PAR2 overexpression reversed these effects and subsequently modulated proinflammatory target genes. Collectively, our data define that PAR2 induces oxidative stress and inflammation through Akt-mediated phosphorylation of NF-κB (Ser536) and FoxO6 (Ser184), which could be a critical upstream regulatory mechanism in ROS-mediated inflammatory response.
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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 Socratic graph.