Premature differentiation of nephron progenitor cell and dysregulation of gene pathways critical to kidney development in a model of preterm birth

Abstract Preterm birth is a leading cause of neonatal morbidity. Survivors have a greater risk for kidney dysfunction and hypertension. Little is known about the molecular changes that occur in the kidney of individuals born preterm. Here, we demonstrate that mice delivered two days prior to full te...

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Autores principales: Aleksandra Cwiek, Masako Suzuki, Kimberly deRonde, Mark Conaway, Kevin M. Bennett, Samir El Dahr, Kimberly J. Reidy, Jennifer R. Charlton
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:18b43f87c303431d9d6ae315e4174c3d2021-11-08T10:53:26ZPremature differentiation of nephron progenitor cell and dysregulation of gene pathways critical to kidney development in a model of preterm birth10.1038/s41598-021-00489-y2045-2322https://doaj.org/article/18b43f87c303431d9d6ae315e4174c3d2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00489-yhttps://doaj.org/toc/2045-2322Abstract Preterm birth is a leading cause of neonatal morbidity. Survivors have a greater risk for kidney dysfunction and hypertension. Little is known about the molecular changes that occur in the kidney of individuals born preterm. Here, we demonstrate that mice delivered two days prior to full term gestation undergo premature cessation of nephrogenesis, resulting in a lower glomerular density. Kidneys from preterm and term groups exhibited differences in gene expression profiles at 20- and 27-days post-conception, including significant differences in the expression of fat-soluble vitamin-related genes. Kidneys of the preterm mice exhibited decreased proportions of endothelial cells and a lower expression of genes promoting angiogenesis compared to the term group. Kidneys from the preterm mice also had altered nephron progenitor subpopulations, early Six2 depletion, and altered Jag1 expression in the nephrogenic zone, consistent with premature differentiation of nephron progenitor cells. In conclusion, preterm birth alone was sufficient to shorten the duration of nephrogenesis and cause premature differentiation of nephron progenitor cells. These candidate genes and pathways may provide targets to improve kidney health in preterm infants.Aleksandra CwiekMasako SuzukiKimberly deRondeMark ConawayKevin M. BennettSamir El DahrKimberly J. ReidyJennifer R. CharltonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Aleksandra Cwiek
Masako Suzuki
Kimberly deRonde
Mark Conaway
Kevin M. Bennett
Samir El Dahr
Kimberly J. Reidy
Jennifer R. Charlton
Premature differentiation of nephron progenitor cell and dysregulation of gene pathways critical to kidney development in a model of preterm birth
description Abstract Preterm birth is a leading cause of neonatal morbidity. Survivors have a greater risk for kidney dysfunction and hypertension. Little is known about the molecular changes that occur in the kidney of individuals born preterm. Here, we demonstrate that mice delivered two days prior to full term gestation undergo premature cessation of nephrogenesis, resulting in a lower glomerular density. Kidneys from preterm and term groups exhibited differences in gene expression profiles at 20- and 27-days post-conception, including significant differences in the expression of fat-soluble vitamin-related genes. Kidneys of the preterm mice exhibited decreased proportions of endothelial cells and a lower expression of genes promoting angiogenesis compared to the term group. Kidneys from the preterm mice also had altered nephron progenitor subpopulations, early Six2 depletion, and altered Jag1 expression in the nephrogenic zone, consistent with premature differentiation of nephron progenitor cells. In conclusion, preterm birth alone was sufficient to shorten the duration of nephrogenesis and cause premature differentiation of nephron progenitor cells. These candidate genes and pathways may provide targets to improve kidney health in preterm infants.
format article
author Aleksandra Cwiek
Masako Suzuki
Kimberly deRonde
Mark Conaway
Kevin M. Bennett
Samir El Dahr
Kimberly J. Reidy
Jennifer R. Charlton
author_facet Aleksandra Cwiek
Masako Suzuki
Kimberly deRonde
Mark Conaway
Kevin M. Bennett
Samir El Dahr
Kimberly J. Reidy
Jennifer R. Charlton
author_sort Aleksandra Cwiek
title Premature differentiation of nephron progenitor cell and dysregulation of gene pathways critical to kidney development in a model of preterm birth
title_short Premature differentiation of nephron progenitor cell and dysregulation of gene pathways critical to kidney development in a model of preterm birth
title_full Premature differentiation of nephron progenitor cell and dysregulation of gene pathways critical to kidney development in a model of preterm birth
title_fullStr Premature differentiation of nephron progenitor cell and dysregulation of gene pathways critical to kidney development in a model of preterm birth
title_full_unstemmed Premature differentiation of nephron progenitor cell and dysregulation of gene pathways critical to kidney development in a model of preterm birth
title_sort premature differentiation of nephron progenitor cell and dysregulation of gene pathways critical to kidney development in a model of preterm birth
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/18b43f87c303431d9d6ae315e4174c3d
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