Cargando…
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...
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1784801238582296576 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9528100 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT mahesaniyaafreeda sexdifferencesinglomerularproteinexpressionandeffectsofsoybaseddietonpodocytesignaling AT williamsoncaseyr sexdifferencesinglomerularproteinexpressionandeffectsofsoybaseddietonpodocytesignaling AT keyvanichahiava sexdifferencesinglomerularproteinexpressionandeffectsofsoybaseddietonpodocytesignaling AT martinclairee sexdifferencesinglomerularproteinexpressionandeffectsofsoybaseddietonpodocytesignaling AT mitroalexandere sexdifferencesinglomerularproteinexpressionandeffectsofsoybaseddietonpodocytesignaling AT lupeihua sexdifferencesinglomerularproteinexpressionandeffectsofsoybaseddietonpodocytesignaling AT newlauraa sexdifferencesinglomerularproteinexpressionandeffectsofsoybaseddietonpodocytesignaling AT watsonkatrinal sexdifferencesinglomerularproteinexpressionandeffectsofsoybaseddietonpodocytesignaling AT mooreheadrogera sexdifferencesinglomerularproteinexpressionandeffectsofsoybaseddietonpodocytesignaling AT jonesnina sexdifferencesinglomerularproteinexpressionandeffectsofsoybaseddietonpodocytesignaling |