Sex and kidney ACE2 expression in primary focal segmental glomerulosclerosis: A NEPTUNE study.

<h4>Background</h4>Angiotensin-converting enzyme 2 (ACE2) has been implicated in the pathogenesis of experimental kidney disease. ACE2 is on the X chromosome, and in mice, deletion of ACE2 leads to the development of focal segmental glomerulosclerosis (FSGS). The relationship between sex...

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Autores principales:	Nicholas A Maksimowski, James W Scholey, Vanessa R Williams, Nephrotic Syndrome Study Network (NEPTUNE)
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6024b2ceef1a4faba81096121cd4777e
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spelling	oai:doaj.org-article:6024b2ceef1a4faba81096121cd4777e2021-12-02T20:07:13ZSex and kidney ACE2 expression in primary focal segmental glomerulosclerosis: A NEPTUNE study.1932-620310.1371/journal.pone.0252758https://doaj.org/article/6024b2ceef1a4faba81096121cd4777e2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0252758https://doaj.org/toc/1932-6203<h4>Background</h4>Angiotensin-converting enzyme 2 (ACE2) has been implicated in the pathogenesis of experimental kidney disease. ACE2 is on the X chromosome, and in mice, deletion of ACE2 leads to the development of focal segmental glomerulosclerosis (FSGS). The relationship between sex and renal ACE2 expression in humans with kidney disease is a gap in current knowledge.<h4>Methods</h4>We studied renal tubulointerstitial microarray data and clinical variables from subjects with FSGS enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) study. We compared relationships between ACE2 expression and age, estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (UACR), interstitial fibrosis, tubular atrophy, and genes implicated in inflammation and fibrosis in male and female subjects.<h4>Results</h4>ACE2 mRNA expression was lower in the tubulointerstitium of males compared to females (P = 0.0026). Multiple linear regression analysis showed that ACE2 expression was related to sex and eGFR but not to age or treatment with renin angiotensin system blockade. ACE2 expression is also related to interstitial fibrosis, and tubular atrophy, in males but not in females. Genes involved in inflammation (CCL2 and TNF) correlated with ACE2 expression in males (TNF: r = -0.65, P < 0.0001; CCL2: r = -0.60, P < 0.0001) but not in females. TGFB1, a gene implicated in fibrosis correlated with ACE2 in both sexes.<h4>Conclusions</h4>Sex is an important determinant of ACE2 expression in the tubulointerstitium of the kidney in FSGS. Sex also influences the relationships between ACE2, kidney fibrosis, and expression of genes involved in kidney inflammation.Nicholas A MaksimowskiJames W ScholeyVanessa R WilliamsNephrotic Syndrome Study Network (NEPTUNE)Public Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0252758 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicholas A Maksimowski James W Scholey Vanessa R Williams Nephrotic Syndrome Study Network (NEPTUNE) Sex and kidney ACE2 expression in primary focal segmental glomerulosclerosis: A NEPTUNE study.
description	<h4>Background</h4>Angiotensin-converting enzyme 2 (ACE2) has been implicated in the pathogenesis of experimental kidney disease. ACE2 is on the X chromosome, and in mice, deletion of ACE2 leads to the development of focal segmental glomerulosclerosis (FSGS). The relationship between sex and renal ACE2 expression in humans with kidney disease is a gap in current knowledge.<h4>Methods</h4>We studied renal tubulointerstitial microarray data and clinical variables from subjects with FSGS enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) study. We compared relationships between ACE2 expression and age, estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (UACR), interstitial fibrosis, tubular atrophy, and genes implicated in inflammation and fibrosis in male and female subjects.<h4>Results</h4>ACE2 mRNA expression was lower in the tubulointerstitium of males compared to females (P = 0.0026). Multiple linear regression analysis showed that ACE2 expression was related to sex and eGFR but not to age or treatment with renin angiotensin system blockade. ACE2 expression is also related to interstitial fibrosis, and tubular atrophy, in males but not in females. Genes involved in inflammation (CCL2 and TNF) correlated with ACE2 expression in males (TNF: r = -0.65, P < 0.0001; CCL2: r = -0.60, P < 0.0001) but not in females. TGFB1, a gene implicated in fibrosis correlated with ACE2 in both sexes.<h4>Conclusions</h4>Sex is an important determinant of ACE2 expression in the tubulointerstitium of the kidney in FSGS. Sex also influences the relationships between ACE2, kidney fibrosis, and expression of genes involved in kidney inflammation.
format	article
author	Nicholas A Maksimowski James W Scholey Vanessa R Williams Nephrotic Syndrome Study Network (NEPTUNE)
author_facet	Nicholas A Maksimowski James W Scholey Vanessa R Williams Nephrotic Syndrome Study Network (NEPTUNE)
author_sort	Nicholas A Maksimowski
title	Sex and kidney ACE2 expression in primary focal segmental glomerulosclerosis: A NEPTUNE study.
title_short	Sex and kidney ACE2 expression in primary focal segmental glomerulosclerosis: A NEPTUNE study.
title_full	Sex and kidney ACE2 expression in primary focal segmental glomerulosclerosis: A NEPTUNE study.
title_fullStr	Sex and kidney ACE2 expression in primary focal segmental glomerulosclerosis: A NEPTUNE study.
title_full_unstemmed	Sex and kidney ACE2 expression in primary focal segmental glomerulosclerosis: A NEPTUNE study.
title_sort	sex and kidney ace2 expression in primary focal segmental glomerulosclerosis: a neptune study.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/6024b2ceef1a4faba81096121cd4777e
work_keys_str_mv	AT nicholasamaksimowski sexandkidneyace2expressioninprimaryfocalsegmentalglomerulosclerosisaneptunestudy AT jameswscholey sexandkidneyace2expressioninprimaryfocalsegmentalglomerulosclerosisaneptunestudy AT vanessarwilliams sexandkidneyace2expressioninprimaryfocalsegmentalglomerulosclerosisaneptunestudy AT nephroticsyndromestudynetworkneptune sexandkidneyace2expressioninprimaryfocalsegmentalglomerulosclerosisaneptunestudy
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Sex and kidney ACE2 expression in primary focal segmental glomerulosclerosis: A NEPTUNE study.

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