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Changes in renal WT-1 expression preceding hypertension development

BACKGROUND: Hypertension is a public health problem with mostly unknown causes, and where strong hereditary genetic alterations have not been fully elucidated. However, the use of experimental models has provided valuable information. Recent evidences suggest that alterations in key nephrogenic fact...

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Autores principales: Mazzei, Luciana, García, Mercedes, Calvo, Juan Pablo, Casarotto, Mariana, Fornés, Miguel, Abud, María Angélica, Cuello-carrión, Darío, Ferder, León, Manucha, Walter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806522/
https://www.ncbi.nlm.nih.gov/pubmed/27009470
http://dx.doi.org/10.1186/s12882-016-0250-6
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author Mazzei, Luciana
García, Mercedes
Calvo, Juan Pablo
Casarotto, Mariana
Fornés, Miguel
Abud, María Angélica
Cuello-carrión, Darío
Ferder, León
Manucha, Walter
author_facet Mazzei, Luciana
García, Mercedes
Calvo, Juan Pablo
Casarotto, Mariana
Fornés, Miguel
Abud, María Angélica
Cuello-carrión, Darío
Ferder, León
Manucha, Walter
author_sort Mazzei, Luciana
collection PubMed
description BACKGROUND: Hypertension is a public health problem with mostly unknown causes, and where strong hereditary genetic alterations have not been fully elucidated. However, the use of experimental models has provided valuable information. Recent evidences suggest that alterations in key nephrogenic factors, such as Wilms’ tumor 1 transcription factor (WT-1), could contribute to the development of hypertension. The aim of this paper is to evaluate the expression of WT-1 and related genes in the nephrogenic process in connection with the development of hypertension as well as the corresponding anatomical and functional correlation. METHODS: Male spontaneously hypertensive and control rats were evaluated weekly from birth until week 8 of life. Their blood pressure was taken weekly using the tail-cuff blood pressure system. Weekly, 5 rats per group were sacrificed with a lethal injection of pentobarbital, and their kidneys were removed, decapsulated and weighed. The serum was collected for measuring biochemical parameters. The results were assessed using one-way analysis of variance for comparisons between groups. RESULTS: The relationship between renal weight/total body weights was established, without significantly different values. These data were compared with apoptosis, fibrosis, number and size of the glomeruli. The elevation of systolic blood pressure was significant since week 6. Biochemical values differed slightly. Histology showed a slight increase in deposits of collagen fibers since week 4. Additionally, in kidney cortices, the expression of WT-1, heat shock protein 70 (Hsp70) and vitamin D receptors (VDR) decreased since week 4. Finally, we demonstrated ultrastructural damage to mitochondria since week 4. CONCLUSIONS: Our results would suggest an unprecedented link, possibly a regulatory mechanism, between WT-1 on nephrogenic alteration processes and their relationship with hypertension. Moreover, and previous to the increase in blood pressure, we demonstrated low expressions of WT-1, VDR and Hsp70 in kidneys from neonatal SHRs. If so, this may suggest that deregulation in the expression of WT-1 and its impact on nephrogenesis induction could be crucial in understanding the development and maintenance of hypertension. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12882-016-0250-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-48065222016-03-25 Changes in renal WT-1 expression preceding hypertension development Mazzei, Luciana García, Mercedes Calvo, Juan Pablo Casarotto, Mariana Fornés, Miguel Abud, María Angélica Cuello-carrión, Darío Ferder, León Manucha, Walter BMC Nephrol Research Article BACKGROUND: Hypertension is a public health problem with mostly unknown causes, and where strong hereditary genetic alterations have not been fully elucidated. However, the use of experimental models has provided valuable information. Recent evidences suggest that alterations in key nephrogenic factors, such as Wilms’ tumor 1 transcription factor (WT-1), could contribute to the development of hypertension. The aim of this paper is to evaluate the expression of WT-1 and related genes in the nephrogenic process in connection with the development of hypertension as well as the corresponding anatomical and functional correlation. METHODS: Male spontaneously hypertensive and control rats were evaluated weekly from birth until week 8 of life. Their blood pressure was taken weekly using the tail-cuff blood pressure system. Weekly, 5 rats per group were sacrificed with a lethal injection of pentobarbital, and their kidneys were removed, decapsulated and weighed. The serum was collected for measuring biochemical parameters. The results were assessed using one-way analysis of variance for comparisons between groups. RESULTS: The relationship between renal weight/total body weights was established, without significantly different values. These data were compared with apoptosis, fibrosis, number and size of the glomeruli. The elevation of systolic blood pressure was significant since week 6. Biochemical values differed slightly. Histology showed a slight increase in deposits of collagen fibers since week 4. Additionally, in kidney cortices, the expression of WT-1, heat shock protein 70 (Hsp70) and vitamin D receptors (VDR) decreased since week 4. Finally, we demonstrated ultrastructural damage to mitochondria since week 4. CONCLUSIONS: Our results would suggest an unprecedented link, possibly a regulatory mechanism, between WT-1 on nephrogenic alteration processes and their relationship with hypertension. Moreover, and previous to the increase in blood pressure, we demonstrated low expressions of WT-1, VDR and Hsp70 in kidneys from neonatal SHRs. If so, this may suggest that deregulation in the expression of WT-1 and its impact on nephrogenesis induction could be crucial in understanding the development and maintenance of hypertension. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12882-016-0250-6) contains supplementary material, which is available to authorized users. BioMed Central 2016-03-24 /pmc/articles/PMC4806522/ /pubmed/27009470 http://dx.doi.org/10.1186/s12882-016-0250-6 Text en © Mazzei et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Mazzei, Luciana
García, Mercedes
Calvo, Juan Pablo
Casarotto, Mariana
Fornés, Miguel
Abud, María Angélica
Cuello-carrión, Darío
Ferder, León
Manucha, Walter
Changes in renal WT-1 expression preceding hypertension development
title Changes in renal WT-1 expression preceding hypertension development
title_full Changes in renal WT-1 expression preceding hypertension development
title_fullStr Changes in renal WT-1 expression preceding hypertension development
title_full_unstemmed Changes in renal WT-1 expression preceding hypertension development
title_short Changes in renal WT-1 expression preceding hypertension development
title_sort changes in renal wt-1 expression preceding hypertension development
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806522/
https://www.ncbi.nlm.nih.gov/pubmed/27009470
http://dx.doi.org/10.1186/s12882-016-0250-6
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