ArticleRedox biology2023
EETs alleviate alveolar epithelial cell senescence by inhibiting endoplasmic reticulum stress through the Trim25/Keap1/Nrf2 axis.
Article in Redox biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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57 citing papers in PubMed, 75 citations in OpenAlex.
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- The mechanism of deubiquitinase USP14 modifying HSP90AA1 to activate NRF2 signaling in lung cancer cell resistance to ferroptosis.Molecular biology reports · 2026Article
- Cellular Senescence and Aging: Mechanisms, Disease Convergence, and Therapeutic Frontiers.MedComm · 2026Review
- NINJ1 plays a vital role in the release of neutrophil extracellular traps during acute lung injury.Cell death & disease · 2026Article
- Article
- PRDX2 Mediates the Neuroprotective Role of Umbilical Cord Blood Exosomes via the CYP2J2/8,9-EET Pathway in Models of Parkinson's Disease.Molecular neurobiology · 2026Article
- Rv1983 promotes mycobacterial dissemination by triggering ferroptosis through GPX4 ubiquitination.Cellular & molecular biology letters · 2026Article
- Defective branched-chain amino acid catabolism promotes pulmonary fibrosis by inducing apoptosis resistance of myofibroblasts in mice.Cell communication and signaling : CCS · 2026Article
- Elevated TRIM25 Impairs Poly (ADP-ribose) Metabolism via PARG Degradation and Mediates Compression-Induced Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ER stress affects proliferation and induces polyploidization of cultured human HaCaT and A431 cells.Histochemistry and cell biology · 2026Article
- Fibroblast growth factor-inducible 14 accelerates pulmonary fibrosis by inducing fibroblast senescence in mice.Cellular and molecular life sciences : CMLS · 2026Article
- CYP1B1 modulates stress and repair pathways in airway cells challenged by wood smoke particles.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Lipid metabolism in homeostasis and disease.Signal transduction and targeted therapy · 2026Review
- Rosmarinic Acid Inhibits PRV Replication by Regulating Oxidative Stress Through the Nrf2 Signaling Pathway.Animals : an open access journal from MDPI · 2026Article
- The Mechanism of Oxidative Stress in Pulmonary Fibrosis and Research Progress.Antioxidants (Basel, Switzerland) · 2026Review
- Novel triterpenoids from Ganoderma resinaceum attenuate UV-induced photoaging via modulating Nrf2 and MAPK signaling pathways.Natural products and bioprospecting · 2026Article
- Oxidative Stress and PRKN-Mediated Senescence Link RhoA/ROCK Signaling to Epithelial Remodeling in Allergic Rhinitis.Antioxidants (Basel, Switzerland) · 2026Article
- TRIM25-mediated ferroptosis resistance is closely associated with poor prognosis in hepatocellular carcinoma.Frontiers in immunology · 2026Article
- Cellular senescence in Crohn's disease: a double-edged sword in intestinal fibrosis.Frontiers in immunology · 2026Review
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Authors and funding
11 authors at 2 institutions in 1 country.
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Abstract
Alveolar epithelial cell (AEC) senescence is a key driver of a variety of chronic lung diseases. It remains a challenge how to alleviate AEC senescence and mitigate disease progression. Our study identified a critical role of epoxyeicosatrienoic acids (EETs), downstream metabolites of arachidonic acid (ARA) by cytochrome p450 (CYP), in alleviating AEC senescence. In vitro, we found that 14,15-EET content was significantly decreased in senescent AECs. Exogenous EETs supplementation, overexpression of CYP2J2, or inhibition of EETs degrading enzyme soluble epoxide hydrolase (sEH) to increase EETs alleviated AECs' senescence. Mechanistically, 14,15-EET promoted the expression of Trim25 to ubiquitinate and degrade Keap1 and promoted Nrf2 to enter the nucleus to exert an anti-oxidant effect, thereby inhibiting endoplasmic reticulum stress (ERS) and alleviating AEC senescence. Furthermore, in D-galactose (D-gal)-induced premature aging mouse model, inhibiting the degradation of EETs by Trifluoromethoxyphenyl propionylpiperidin urea (TPPU, an inhibitor of sEH) significantly inhibited the protein expression of p16, p21, and γH2AX. Meanwhile, TPPU reduced the degree of age-related pulmonary fibrosis in mice. Our study has confirmed that EETs are novel anti-senescence substances for AECs, providing new targets for the treatment of chronic lung diseases.
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