ERMP1 as a newly identified ER stress gatekeeper in chronic kidney disease

Article Article scientifique Article ERMP1 as a newly identified ER stress gatekeeper in chronic kidney disease eng 2025-01-28 2025-03 author Correia De Sousa Marta Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 910172 Département de physiologie cellulaire et métabolisme (PHYME) author Arnoux Grégoire Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 674746 author Yvon Raphaël Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 416762 Département de physiologie cellulaire et métabolisme (PHYME) author Maeder Garavaglia Christine Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 22210 Département de physiologie cellulaire et métabolisme (PHYME) author Fournier Margot Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 134287 Département de physiologie cellulaire et métabolisme (PHYME) author Morin Noëlie Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 977257 Unité de formation des apprentis (UFA) author Dolicka Dobrochna Dorota Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 842579 author Delangre Etienne Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 983567 Département de physiologie cellulaire et métabolisme (PHYME) author Tuerkal Miranda Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 402574 Département de physiologie cellulaire et métabolisme (PHYME) author Charlemagne Thibaut Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 407809 Département de physiologie cellulaire et métabolisme (PHYME) author De Seigneux Matthey Sophie 0000-0002-4243-366X Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.,Department of Medicine, Laboratory of Nephrology, University Hospitals of Geneva, Geneva, Switzerland. 105798 Département de médecine (DEMED) author Legouis David 0000-0002-2924-9737 Department of Acute Medicine, Division of Intensive Care, University Hospitals of Geneva, Geneva, Switzerland.,Department of Medicine, Laboratory of Nephrology, University Hospitals of Geneva, Geneva, Switzerland. 883952 Département d'anesthésiologie, pharmacologie et soins intensifs (APSIC) author Maechler Pierre 0000-0002-2005-1433 Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 76515 Département de physiologie cellulaire et métabolisme (PHYME) author Feraille Eric 0000-0003-1656-8365 Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 27356 Département de physiologie cellulaire et métabolisme (PHYME) author Foti Michelangelo 0000-0001-7199-4135 Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 28033 author Gjorgjieva Ducros Monika 0000-0001-8553-7525 Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 891816 Département de physiologie cellulaire et métabolisme (PHYME) Monika Gjorgjieva F375-F388 10.1152/ajprenal.00159.2024 39873175 1522-1466 https://journals.physiology.org/doi/full/10.1152/ajprenal.00159.2024 ERMP1 is involved in the Unfolded Protein Response (UPR) pathway in response to endoplasmic reticulum (ER) stress. Given the pivotal role of ER stress in the pathogenesis of acute and chronic kidney diseases, we hypothesized that ERMP1 could be instrumental in the development of renal injury. In silico analysis of RNA sequencing datasets from renal biopsies were exploited to assess the expression of ERMP1 in the kidney under normal or pathological conditions. CRISPR-Cas9- mediated heterozygous genetic ablation of the exon 1 of Ermp1 was performed in vivo , followed by histological analysis and assessment of renal injury and ER stress markers in the newly generated Ermp1 knockout mouse model. Additionally, knockdown and overexpression of ERMP1 were conducted in human tubular cells to investigate cell viability, metabolism, the UPR pathway and ER Ca2+ release under these conditions. Our findings from patient datasets showed that ERMP1 is expressed in all renal cell types and is upregulated in chronic kidney disease. Further in silico investigations suggest a role for ERMP1 in renal development. ERMP1 knockout in mice revealed that homozygous loss of ERMP1 expression is lethal, while heterozygous loss exacerbated age-related chronic kidney alteration. In human tubular cells, ERMP1 knockdown decreased viability and metabolic rate, whereas overexpression conferred protection against ER stress. These results highlight the importance of ERMP1 in renal physiology and pathology and suggest that its upregulation could be a protective mechanism against excessive ER stress in renal tubule epithelial cells. ER stress ERMP1 Chronic kidney disease Dewey 612 Dewey 616 Dewey 617 Fondation Gustave et Simone Prévot (Fondation Prévot) NA Swiss National Science Foundation Tumour bioenergetic: ERMP1 in MAFLD-driven liver cancer 215041 CH Projects 134 Département de physiologie cellulaire et métabolisme 21C 56 Département de médecine 221 63 Département d'anesthésiologie, pharmacologie, soins intensifs et urgences 229 false 472 Obésité et syndrome métabolique 803 897 Insuffisance rénale chronique 941 402 Mitochondries et métabolisme énergétique 671 20 Laboratoire de physiologie et pathophysiologie des cellules rénales 29 https://yareta.unige.ch/archives/45c96f09-d4c3-4002-9fed-304451659ae0 American journal of physiology. Renal physiology 328 3 586b1363-c405-43fe-adc1-0f6cc63b8879 Article (Published version) Public correia-de-sousa-et-al-2025-ermp1-a.pdf 6216579 application/pdf CC BY-4.0 2ca6e37073562a8ee676caa86cfda738936887a1ef796a6681355072cdf599d2 66109424-af04-45ec-a3a9-82ceda802edf Supplemental data Public Supplem_Mat.pdf 2792644 application/pdf CC BY-4.0 5d17f20954a06ae4e292ab989de1948afe727ac02ea5d805121fc019de2103b8 Vignette Public ajprenal.00159.2024_f0-1.png 199192 image/png openAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine clinique / Département d'anesthésiologie, pharmacologie, soins intensifs et urgences

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ERMP1 as a newly identified ER stress gatekeeper in chronic kidney disease	American journal of physiology. Renal physiology			2025	115	132

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