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Loss of Ecrg4 improves calcium oxalate nephropathy

Kidney stone is one of the most frequent urinary tract diseases, affecting 10% of the population and displaying a high recurrence rate. Kidney stones are the result of salt supersaturation, including calcium and oxalate. We have previously identified Esophageal cancer-related gene 4 (Ecrg4) as being...

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Autores principales: Cabuzu, Daniela, Ramakrishnan, Suresh K., Moor, Matthias B., Harmacek, Dusan, Auberson, Muriel, Durussel, Fanny, Bonny, Olivier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9560046/
https://www.ncbi.nlm.nih.gov/pubmed/36227903
http://dx.doi.org/10.1371/journal.pone.0275972
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author Cabuzu, Daniela
Ramakrishnan, Suresh K.
Moor, Matthias B.
Harmacek, Dusan
Auberson, Muriel
Durussel, Fanny
Bonny, Olivier
author_facet Cabuzu, Daniela
Ramakrishnan, Suresh K.
Moor, Matthias B.
Harmacek, Dusan
Auberson, Muriel
Durussel, Fanny
Bonny, Olivier
author_sort Cabuzu, Daniela
collection PubMed
description Kidney stone is one of the most frequent urinary tract diseases, affecting 10% of the population and displaying a high recurrence rate. Kidney stones are the result of salt supersaturation, including calcium and oxalate. We have previously identified Esophageal cancer-related gene 4 (Ecrg4) as being modulated by hypercalciuria. Ecrg4 was initially described as a tumor suppressor gene in the esophagus. Lately, it was shown to be involved as well in apoptosis, cell senescence, cell migration, inflammation and cell responsiveness to chemotherapy. To the best of our knowledge, nothing is known about ECRG4’s function in the renal tissue and its relationship with calciuria. We hypothesized that the increased expression of Ecrg4 mRNA is triggered by hypercalciuria and might modulate intratubular calcium-oxalate precipitation. In this study, we have first (i) validated the increased Ecrg4 mRNA in several types of hypercalciuric mouse models, then (ii) described the Ecrg4 mRNA expression along the nephron and (iii) assessed ECRG4’s putative role in calcium oxalate nephropathy. For this, Ecrg4 KO mice were challenged with a kidney stone-inducing diet, rich in calcium and oxalate precursor. Taken together, our study demonstrates that Ecrg4’s expression is restricted mainly to the distal part of the nephron and that the Ecrg4 KO mice develop less signs of tubular obstruction and less calcium-oxalate deposits. This promotes Ecrg4 as a modulator of renal crystallization and may open the way to new therapeutic possibilities against calcium oxalate nephropathy.
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spelling pubmed-95600462022-10-14 Loss of Ecrg4 improves calcium oxalate nephropathy Cabuzu, Daniela Ramakrishnan, Suresh K. Moor, Matthias B. Harmacek, Dusan Auberson, Muriel Durussel, Fanny Bonny, Olivier PLoS One Research Article Kidney stone is one of the most frequent urinary tract diseases, affecting 10% of the population and displaying a high recurrence rate. Kidney stones are the result of salt supersaturation, including calcium and oxalate. We have previously identified Esophageal cancer-related gene 4 (Ecrg4) as being modulated by hypercalciuria. Ecrg4 was initially described as a tumor suppressor gene in the esophagus. Lately, it was shown to be involved as well in apoptosis, cell senescence, cell migration, inflammation and cell responsiveness to chemotherapy. To the best of our knowledge, nothing is known about ECRG4’s function in the renal tissue and its relationship with calciuria. We hypothesized that the increased expression of Ecrg4 mRNA is triggered by hypercalciuria and might modulate intratubular calcium-oxalate precipitation. In this study, we have first (i) validated the increased Ecrg4 mRNA in several types of hypercalciuric mouse models, then (ii) described the Ecrg4 mRNA expression along the nephron and (iii) assessed ECRG4’s putative role in calcium oxalate nephropathy. For this, Ecrg4 KO mice were challenged with a kidney stone-inducing diet, rich in calcium and oxalate precursor. Taken together, our study demonstrates that Ecrg4’s expression is restricted mainly to the distal part of the nephron and that the Ecrg4 KO mice develop less signs of tubular obstruction and less calcium-oxalate deposits. This promotes Ecrg4 as a modulator of renal crystallization and may open the way to new therapeutic possibilities against calcium oxalate nephropathy. Public Library of Science 2022-10-13 /pmc/articles/PMC9560046/ /pubmed/36227903 http://dx.doi.org/10.1371/journal.pone.0275972 Text en © 2022 Cabuzu et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Cabuzu, Daniela
Ramakrishnan, Suresh K.
Moor, Matthias B.
Harmacek, Dusan
Auberson, Muriel
Durussel, Fanny
Bonny, Olivier
Loss of Ecrg4 improves calcium oxalate nephropathy
title Loss of Ecrg4 improves calcium oxalate nephropathy
title_full Loss of Ecrg4 improves calcium oxalate nephropathy
title_fullStr Loss of Ecrg4 improves calcium oxalate nephropathy
title_full_unstemmed Loss of Ecrg4 improves calcium oxalate nephropathy
title_short Loss of Ecrg4 improves calcium oxalate nephropathy
title_sort loss of ecrg4 improves calcium oxalate nephropathy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9560046/
https://www.ncbi.nlm.nih.gov/pubmed/36227903
http://dx.doi.org/10.1371/journal.pone.0275972
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