ArticleCell death discovery2021
Downregulation of XBP1 protects kidney against ischemia-reperfusion injury via suppressing HRD1-mediated NRF2 ubiquitylation.
Article in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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The trial behind it
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Who cites it
39 citing papers in PubMed, 59 citations in OpenAlex.
- Guaianolide dimer KGA-1002 targets GRP94 and triggers unfolded protein response-associated degradation of SKP2/AKT axis as a novel antihepatoma agent.Journal of advanced research · 2026Article
- Caveolin-1 Stabilizes SERCA2 to Counteract Acute Kidney Injury via Suppression of CaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Redox control at the ER-mitochondria interface in kidney transplantation: MAM-centered stress signaling and translational organoid platforms.Redox biology · 2026Review
- Natural compounds targeting inflammatory signaling and cell adhesion molecules in ischemic acute kidney injury.Archives of pharmacal research · 2026Review
- Crosstalk Between the NRF2 Signaling Pathway and Heat Shock Proteins: Implications for Cellular Stress Response and Disease Therapy.Oxidative medicine and cellular longevity · 2026Review
- Oxidative stress and endoplasmic reticulum stress in acute kidney injury: mechanistic crosstalk and therapeutic modulation.Frontiers in medicine · 2026Review
- XBP1s-Orchestrated Soluble Mediators: Participants of Oxidative Stress in Renal Ischemia-Reperfusion Injury Following Donation After Circulatory Death.Mediators of inflammation · 2026Review
- Bacteroides uniformis-generated hexadecanedioic acid ameliorates metabolic-associated fatty liver disease.Gut microbes · 2025Article
- Intermodulation of endoplasmic reticulum stress and ferroptosis in diabetic nephropathy: molecular mechanisms and therapeutic potentials.Apoptosis : an international journal on programmed cell death · 2025Review
- Targeting epigenetic and post-translational modifications of NRF2: key regulatory factors in disease treatment.Cell death discovery · 2025Review
- Targeting the Interplay Between Autophagy and the Nrf2 Pathway in Parkinson's Disease with Potential Therapeutic Implications.Biomolecules · 2025Review
- The role of ubiquitination and deubiquitination in urological tumours.Frontiers in pharmacology · 2025Review
- Puerarin alleviates renal ischemia/reperfusion injury by inhibiting apoptosis and endoplasmic reticulum stress via Nrf2/HO-1 pathway.Iranian journal of basic medical sciences · 2025Article
- A Low Expression of NRF2 Enhances Oxidative Stress and Autophagy in Myofibroblasts, Promoting Progression of Chronic Obstructive Pulmonary Disease.Current medicinal chemistry · 2025Article
- The USP11/Nrf2 positive feedback loop promotes colorectal cancer progression by inhibiting mitochondrial apoptosis.Cell death & disease · 2024Article
- Sex-specific molecular signature of mouse podocytes in homeostasis and in response to pharmacological challenge with rapamycin.Biology of sex differences · 2024Article
- Casting Light on the Janus-Faced HMG-CoA Reductase Degradation Protein 1: A Comprehensive Review of Its Dualistic Impact on Apoptosis in Various Diseases.Molecular neurobiology · 2024Review
- Selenium nanoparticles alleviate renal ischemia/reperfusion injury by inhibiting ferritinophagy via the XBP1/NCOA4 pathway.Cell communication and signaling : CCS · 2024Article
- Endoplasmic reticulum stress signaling modulates ischemia/reperfusion injury in the aged heart by regulating mitochondrial maintenance.Molecular medicine (Cambridge, Mass.) · 2024Review
- Comprehensive overview of the role of mitochondrial dysfunction in the pathogenesis of acute kidney ischemia-reperfusion injury: a narrative review.Journal of Yeungnam medical science · 2024Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Ischemia-reperfusion (IR) injury to the renal epithelia is associated with endoplasmic reticulum stress (ERS) and mitochondria dysfunction, which lead to oxidative stress-induced acute kidney injury (AKI). X-box binding protein 1 (XBP1), an ERS response protein, could play a prominent role in IR-induced AKI. In this study, we revealed that XBP1 and its downstream target HRD1 participated in the crosstalk between ERS and mitochondrial dysfunction via regulation of NRF2/HO-1-mediated reactive oxidative stress (ROS) signaling. Mice with reduced expression of XBP1 (heterozygous Xbp1±) were resistant to IR-induced AKI due to the enhanced expression of NRF2/HO-1 and diminished ROS in the kidney. Downregulation of XBP1 in renal epithelial cells resulted in reduced HRD1 expression and increased NRF2/HO-1 function, accompanied with enhanced antioxidant response. Furthermore, HRD1 served as an E3-ligase to facilitate the downregulation of NRF2 through ubiquitination-degradation pathway, and the QSLVPDI motif on NRF2 constituted an active site for its interaction with HRD1. Thus, our findings unveil an important physiological role for XBP1/HRD1 in modulating the antioxidant function of NRF2/HO-1 in the kidney under stress conditions. Molecular therapeutic approaches that target XBP1-HRD1-NRF2 pathway may represent potential effective means to treat renal IR injury.
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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.