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Profiling renal sodium transporters in mice with nephron Ift88 disruption: Association with sex, cysts, and blood pressure

Loss of nephron primary cilia due to disruption of the Ift88 gene results in sex‐ and age‐specific phenotypes involving renal cystogenesis, blood pressure (BP) and urinary Na(+) excretion. Previous studies demonstrated that male mice undergoing induction of nephron‐specific Ift88 gene disruption at...

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Autores principales: Hu, Chunyan, Lakshmipathi, Jayalakshmi, Stuart, Deborah, Kohan, Donald E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8915723/
https://www.ncbi.nlm.nih.gov/pubmed/35274831
http://dx.doi.org/10.14814/phy2.15206
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author Hu, Chunyan
Lakshmipathi, Jayalakshmi
Stuart, Deborah
Kohan, Donald E.
author_facet Hu, Chunyan
Lakshmipathi, Jayalakshmi
Stuart, Deborah
Kohan, Donald E.
author_sort Hu, Chunyan
collection PubMed
description Loss of nephron primary cilia due to disruption of the Ift88 gene results in sex‐ and age‐specific phenotypes involving renal cystogenesis, blood pressure (BP) and urinary Na(+) excretion. Previous studies demonstrated that male mice undergoing induction of nephron‐specific Ift88 gene disruption at 2 months of age developed reduced BP and increased salt‐induced natriuresis when pre‐cystic (2 months post‐induction) and became hypertensive associated with frankly cystic kidneys by 9 months post‐induction; in contrast, female Ift88 KO mice manifested no unique phenotype 2 months post‐induction and had mildly reduced BP 9 months post‐induction. The current study utilized these Ift88 KO mice to investigate associated changes in renal Na(+) transporter and channel protein expression. At 2 months post‐induction, pre‐cystic male Ift88 KO mice had reduced high salt diet associated total NKCC2 levels while female mice had no alterations in Na(+) transporters or channels. At 9 months post‐induction, cystic male Ift88 KO mice had increased total and phosphorylated NHE3 levels together with reduced NKCC2, phosphorylated and/or total NCC, and ENaC‐α expression on normal and high salt diets. In contrast, female Ift88 KO mice at 9 months post‐induction had no changes in Na(+) transporters or channels beyond an increase in phosphorylated‐NCC during high salt intake. Thus, reduced BP in pre‐cystic, and elevated BP in renal cystic, male Ift88 KO mice are associated with unique sex‐dependent changes in nephron Na(+) transporter/channel expression.
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spelling pubmed-89157232022-03-18 Profiling renal sodium transporters in mice with nephron Ift88 disruption: Association with sex, cysts, and blood pressure Hu, Chunyan Lakshmipathi, Jayalakshmi Stuart, Deborah Kohan, Donald E. Physiol Rep Original Articles Loss of nephron primary cilia due to disruption of the Ift88 gene results in sex‐ and age‐specific phenotypes involving renal cystogenesis, blood pressure (BP) and urinary Na(+) excretion. Previous studies demonstrated that male mice undergoing induction of nephron‐specific Ift88 gene disruption at 2 months of age developed reduced BP and increased salt‐induced natriuresis when pre‐cystic (2 months post‐induction) and became hypertensive associated with frankly cystic kidneys by 9 months post‐induction; in contrast, female Ift88 KO mice manifested no unique phenotype 2 months post‐induction and had mildly reduced BP 9 months post‐induction. The current study utilized these Ift88 KO mice to investigate associated changes in renal Na(+) transporter and channel protein expression. At 2 months post‐induction, pre‐cystic male Ift88 KO mice had reduced high salt diet associated total NKCC2 levels while female mice had no alterations in Na(+) transporters or channels. At 9 months post‐induction, cystic male Ift88 KO mice had increased total and phosphorylated NHE3 levels together with reduced NKCC2, phosphorylated and/or total NCC, and ENaC‐α expression on normal and high salt diets. In contrast, female Ift88 KO mice at 9 months post‐induction had no changes in Na(+) transporters or channels beyond an increase in phosphorylated‐NCC during high salt intake. Thus, reduced BP in pre‐cystic, and elevated BP in renal cystic, male Ift88 KO mice are associated with unique sex‐dependent changes in nephron Na(+) transporter/channel expression. John Wiley and Sons Inc. 2022-03-11 /pmc/articles/PMC8915723/ /pubmed/35274831 http://dx.doi.org/10.14814/phy2.15206 Text en © 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Hu, Chunyan
Lakshmipathi, Jayalakshmi
Stuart, Deborah
Kohan, Donald E.
Profiling renal sodium transporters in mice with nephron Ift88 disruption: Association with sex, cysts, and blood pressure
title Profiling renal sodium transporters in mice with nephron Ift88 disruption: Association with sex, cysts, and blood pressure
title_full Profiling renal sodium transporters in mice with nephron Ift88 disruption: Association with sex, cysts, and blood pressure
title_fullStr Profiling renal sodium transporters in mice with nephron Ift88 disruption: Association with sex, cysts, and blood pressure
title_full_unstemmed Profiling renal sodium transporters in mice with nephron Ift88 disruption: Association with sex, cysts, and blood pressure
title_short Profiling renal sodium transporters in mice with nephron Ift88 disruption: Association with sex, cysts, and blood pressure
title_sort profiling renal sodium transporters in mice with nephron ift88 disruption: association with sex, cysts, and blood pressure
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8915723/
https://www.ncbi.nlm.nih.gov/pubmed/35274831
http://dx.doi.org/10.14814/phy2.15206
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