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...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0275972 |
| _version_ | 1828096074012688384 |
|---|---|
| author | Daniela Cabuzu Suresh K Ramakrishnan Matthias B Moor Dusan Harmacek Muriel Auberson Fanny Durussel Olivier Bonny |
| author_facet | Daniela Cabuzu Suresh K Ramakrishnan Matthias B Moor Dusan Harmacek Muriel Auberson Fanny Durussel Olivier Bonny |
| author_sort | Daniela Cabuzu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T07:24:33Z |
| format | Article |
| id | doaj.art-9ded3e393dd54ca68ee232f6cf7d9910 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-11T07:24:33Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9ded3e393dd54ca68ee232f6cf7d99102022-12-22T04:37:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-011710e027597210.1371/journal.pone.0275972Loss of Ecrg4 improves calcium oxalate nephropathy.Daniela CabuzuSuresh K RamakrishnanMatthias B MoorDusan HarmacekMuriel AubersonFanny DurusselOlivier BonnyKidney 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.https://doi.org/10.1371/journal.pone.0275972 |
| spellingShingle | Daniela Cabuzu Suresh K Ramakrishnan Matthias B Moor Dusan Harmacek Muriel Auberson Fanny Durussel Olivier Bonny Loss of Ecrg4 improves calcium oxalate nephropathy. PLoS ONE |
| 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 |
| url | https://doi.org/10.1371/journal.pone.0275972 |
| work_keys_str_mv | AT danielacabuzu lossofecrg4improvescalciumoxalatenephropathy AT sureshkramakrishnan lossofecrg4improvescalciumoxalatenephropathy AT matthiasbmoor lossofecrg4improvescalciumoxalatenephropathy AT dusanharmacek lossofecrg4improvescalciumoxalatenephropathy AT murielauberson lossofecrg4improvescalciumoxalatenephropathy AT fannydurussel lossofecrg4improvescalciumoxalatenephropathy AT olivierbonny lossofecrg4improvescalciumoxalatenephropathy |