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Sex Differences in Glomerular Protein Expression and Effects of Soy-Based Diet on Podocyte Signaling

BACKGROUND: Kidney disease is a major public health issue arising from loss of glomerular podocyte function, and there are considerable sex differences in its prognosis. Evidence suggests a renoprotective effect of estrogen and soy diet-derived phytoestrogens, although the molecular basis for this i...

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Autores principales: Mahesaniya, Afreeda, Williamson, Casey R., Keyvani Chahi, Ava, Martin, Claire E., Mitro, Alexander E., Lu, Peihua, New, Laura A., Watson, Katrina L., Moorehead, Roger A., Jones, Nina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9528100/
https://www.ncbi.nlm.nih.gov/pubmed/36199279
http://dx.doi.org/10.1177/20543581221121636
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author Mahesaniya, Afreeda
Williamson, Casey R.
Keyvani Chahi, Ava
Martin, Claire E.
Mitro, Alexander E.
Lu, Peihua
New, Laura A.
Watson, Katrina L.
Moorehead, Roger A.
Jones, Nina
author_facet Mahesaniya, Afreeda
Williamson, Casey R.
Keyvani Chahi, Ava
Martin, Claire E.
Mitro, Alexander E.
Lu, Peihua
New, Laura A.
Watson, Katrina L.
Moorehead, Roger A.
Jones, Nina
author_sort Mahesaniya, Afreeda
collection PubMed
description BACKGROUND: Kidney disease is a major public health issue arising from loss of glomerular podocyte function, and there are considerable sex differences in its prognosis. Evidence suggests a renoprotective effect of estrogen and soy diet-derived phytoestrogens, although the molecular basis for this is poorly understood. OBJECTIVE: Here, we aim to assess sex differences in expression of key proteins associated with podocyte survival and determine the effects of dietary soy on glomerular and podocyte signaling. METHODS: Male and female FVB mice were fed control, low (1%), and high (20%) doses of isolated soy protein (ISP) in utero and until 100 days of age. Spot urine was collected to measure proteinuria and isolated glomeruli were used to quantify activated and total levels of nephrin, Akt, and ERK1/2. To investigate protective effects of specific soy phytoestrogens, cultured podocytes were treated with or without daidzein and subject to control or high glucose as a model of podocyte injury. RESULTS: Nephrin and Akt were elevated at baseline in glomeruli from females compared to males. Both sexes that were fed 1% and 20% ISP displayed robust increases in total glomerular Akt compared to controls, and these effects were more prominent in females. A similar trend at both doses in both sexes was observed with activated Akt and total nephrin. Notably, males exclusively showed increased phosphorylation of nephrin and extracellular signal-regulated kinase (ERK) at the 1% ISP dose; however, no overt changes in urinary albumin excretion or podocin levels were observed, suggesting that the soy diets did not impair podocyte function. Finally, in cultured male and female podocytes, daidzein treatment suppressed high glucose-induced ERK activation. CONCLUSIONS: Together, our findings reveal a putative mechanism to explain the protective influence of sex on kidney disease progression, and they provide further evidence to support a beneficial role for dietary soy in preserving glomerular function.
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spelling pubmed-95281002022-10-04 Sex Differences in Glomerular Protein Expression and Effects of Soy-Based Diet on Podocyte Signaling Mahesaniya, Afreeda Williamson, Casey R. Keyvani Chahi, Ava Martin, Claire E. Mitro, Alexander E. Lu, Peihua New, Laura A. Watson, Katrina L. Moorehead, Roger A. Jones, Nina Can J Kidney Health Dis Original Basic Research BACKGROUND: Kidney disease is a major public health issue arising from loss of glomerular podocyte function, and there are considerable sex differences in its prognosis. Evidence suggests a renoprotective effect of estrogen and soy diet-derived phytoestrogens, although the molecular basis for this is poorly understood. OBJECTIVE: Here, we aim to assess sex differences in expression of key proteins associated with podocyte survival and determine the effects of dietary soy on glomerular and podocyte signaling. METHODS: Male and female FVB mice were fed control, low (1%), and high (20%) doses of isolated soy protein (ISP) in utero and until 100 days of age. Spot urine was collected to measure proteinuria and isolated glomeruli were used to quantify activated and total levels of nephrin, Akt, and ERK1/2. To investigate protective effects of specific soy phytoestrogens, cultured podocytes were treated with or without daidzein and subject to control or high glucose as a model of podocyte injury. RESULTS: Nephrin and Akt were elevated at baseline in glomeruli from females compared to males. Both sexes that were fed 1% and 20% ISP displayed robust increases in total glomerular Akt compared to controls, and these effects were more prominent in females. A similar trend at both doses in both sexes was observed with activated Akt and total nephrin. Notably, males exclusively showed increased phosphorylation of nephrin and extracellular signal-regulated kinase (ERK) at the 1% ISP dose; however, no overt changes in urinary albumin excretion or podocin levels were observed, suggesting that the soy diets did not impair podocyte function. Finally, in cultured male and female podocytes, daidzein treatment suppressed high glucose-induced ERK activation. CONCLUSIONS: Together, our findings reveal a putative mechanism to explain the protective influence of sex on kidney disease progression, and they provide further evidence to support a beneficial role for dietary soy in preserving glomerular function. SAGE Publications 2022-09-30 /pmc/articles/PMC9528100/ /pubmed/36199279 http://dx.doi.org/10.1177/20543581221121636 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Basic Research
Mahesaniya, Afreeda
Williamson, Casey R.
Keyvani Chahi, Ava
Martin, Claire E.
Mitro, Alexander E.
Lu, Peihua
New, Laura A.
Watson, Katrina L.
Moorehead, Roger A.
Jones, Nina
Sex Differences in Glomerular Protein Expression and Effects of Soy-Based Diet on Podocyte Signaling
title Sex Differences in Glomerular Protein Expression and Effects of Soy-Based Diet on Podocyte Signaling
title_full Sex Differences in Glomerular Protein Expression and Effects of Soy-Based Diet on Podocyte Signaling
title_fullStr Sex Differences in Glomerular Protein Expression and Effects of Soy-Based Diet on Podocyte Signaling
title_full_unstemmed Sex Differences in Glomerular Protein Expression and Effects of Soy-Based Diet on Podocyte Signaling
title_short Sex Differences in Glomerular Protein Expression and Effects of Soy-Based Diet on Podocyte Signaling
title_sort sex differences in glomerular protein expression and effects of soy-based diet on podocyte signaling
topic Original Basic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9528100/
https://www.ncbi.nlm.nih.gov/pubmed/36199279
http://dx.doi.org/10.1177/20543581221121636
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