ArticleScientific reports2020
Activation of pH-Sensing Receptor OGR1 (GPR68) Induces ER Stress Via the IRE1α/JNK Pathway in an Intestinal Epithelial Cell Model.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 59 citations in OpenAlex.
- Genomic Insights into Winter Wheat Breeding for Severely Cold Climates.International journal of molecular sciences · 2026Article
- Targeting GPR68 Alleviates Inflammation and Lipid Accumulation in Metabolic Dysfunction-Associated Steatohepatitis.Biology · 2026Article
- Joint Acidosis and GPR68 Signaling in Osteoarthritis: Implications for Cartilage Gene Regulation.Genes · 2026Review
- Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression.Biomarker research · 2025Review
- Site-Directed Mutagenesis and Time-Resolved Fluorescence Spectroscopy Reveal That Two Hydrogen-Bonded Carboxylic Side Chains Are Essential for GPR68 Proton Sensing and G Protein Binding.ACS pharmacology & translational science · 2025Article
- Proton-Sensing G Protein-Coupled Receptors and Their Potential Role in Exercise Regulation of Arterial Function.Biomolecules · 2025Review
- Dys-regulated phosphatidylserine externalization as a cell intrinsic immune escape mechanism in cancer.Cell communication and signaling : CCS · 2025Review
- Endoplasmic Reticulum Stress: Triggers Microenvironmental Regulation and Drives Tumor Evolution.Cancer medicine · 2025Review
- Basal State Calibration of a Chemical Reaction Network Model for Autophagy.International journal of molecular sciences · 2024Article
- GPR116 alleviates acetaminophen-induced liver injury in mice by inhibiting endoplasmic reticulum stress.Cellular and molecular life sciences : CMLS · 2024Article
- Immunomodulation of Proton-activated G Protein-coupled Receptors in Inflammation.Current medical science · 2024Review
- Role of pH-sensing receptors in colitis.Pflugers Archiv : European journal of physiology · 2024Review
- Tumorous IRE1α facilitates CD8Cell communication and signaling : CCS · 2024Article
- OGR1 (GPR68) and TDAG8 (GPR65) Have Antagonistic Effects in Models of Colonic Inflammation.International journal of molecular sciences · 2023Article
- Article
- The crosstalk among the physical tumor microenvironment and the effects of glucose deprivation on tumors in the past decade.Frontiers in cell and developmental biology · 2023Review
- The Role of the Hypoxia-Related Unfolded Protein Response (UPR) in the Tumor Microenvironment.Cancers · 2022Review
- Article
- Dezocine induces apoptosis in human cervical carcinoma Hela cells via the endoplasmic reticulum stress pathway.Toxicology research · 2022Article
- Lipogenesis mediated by OGR1 regulates metabolic adaptation to acid stress in cancer cells via autophagy.Cell reports · 2022Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proton-sensing ovarian cancer G-protein coupled receptor (OGR1) plays an important role in pH homeostasis. Acidosis occurs at sites of intestinal inflammation and can induce endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), an evolutionary mechanism that enables cells to cope with stressful conditions. ER stress activates autophagy, and both play important roles in gut homeostasis and contribute to the pathogenesis of inflammatory bowel disease (IBD). Using a human intestinal epithelial cell model, we investigated whether our previously observed protective effects of OGR1 deficiency in experimental colitis are associated with a differential regulation of ER stress, the UPR and autophagy. Caco-2 cells stably overexpressing OGR1 were subjected to an acidic pH shift. pH-dependent OGR1-mediated signalling led to a significant upregulation in the ER stress markers, binding immunoglobulin protein (BiP) and phospho-inositol required 1α (IRE1α), which was reversed by a novel OGR1 inhibitor and a c-Jun N-terminal kinase (JNK) inhibitor. Proton-activated OGR1-mediated signalling failed to induce apoptosis, but triggered accumulation of total microtubule-associated protein 1 A/1B-light chain 3, suggesting blockage of late stage autophagy. Our results show novel functions for OGR1 in the regulation of ER stress through the IRE1α-JNK signalling pathway, as well as blockage of autophagosomal degradation. OGR1 inhibition might represent a novel therapeutic approach in IBD.
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