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Effects of Environmental Conditions on Nephron Number: Modeling Maternal Disease and Epigenetic Regulation in Renal Development

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Effects of Environmental Conditions on Nephron Number: Modeling Maternal Disease and Epigenetic Regulation in Renal Development. / Fuhrmann, Lars; Lindner, Saskia; Hauser, Alexander-Thomas; Höse, Clemens; Kretz, Oliver; Cohen, Clemens D; Lindenmeyer, Maja T; Sippl, Wolfgang; Jung, Manfred; Huber, Tobias B; Wanner, Nicola.

In: INT J MOL SCI, Vol. 22, No. 8, 4157, 16.04.2021.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Fuhrmann, L, Lindner, S, Hauser, A-T, Höse, C, Kretz, O, Cohen, CD, Lindenmeyer, MT, Sippl, W, Jung, M, Huber, TB & Wanner, N 2021, 'Effects of Environmental Conditions on Nephron Number: Modeling Maternal Disease and Epigenetic Regulation in Renal Development', INT J MOL SCI, vol. 22, no. 8, 4157. https://doi.org/10.3390/ijms22084157

APA

Fuhrmann, L., Lindner, S., Hauser, A-T., Höse, C., Kretz, O., Cohen, C. D., Lindenmeyer, M. T., Sippl, W., Jung, M., Huber, T. B., & Wanner, N. (2021). Effects of Environmental Conditions on Nephron Number: Modeling Maternal Disease and Epigenetic Regulation in Renal Development. INT J MOL SCI, 22(8), [4157]. https://doi.org/10.3390/ijms22084157

Vancouver

Fuhrmann L, Lindner S, Hauser A-T, Höse C, Kretz O, Cohen CD et al. Effects of Environmental Conditions on Nephron Number: Modeling Maternal Disease and Epigenetic Regulation in Renal Development. INT J MOL SCI. 2021 Apr 16;22(8). 4157. https://doi.org/10.3390/ijms22084157

Bibtex

@article{41554ac3df1f49a59e15a34d4d18afb1,
title = "Effects of Environmental Conditions on Nephron Number: Modeling Maternal Disease and Epigenetic Regulation in Renal Development",
abstract = "A growing body of evidence suggests that low nephron numbers at birth can increase the risk of chronic kidney disease or hypertension later in life. Environmental stressors, such as maternal malnutrition, medication and smoking, can influence renal size at birth. Using metanephric organ cultures to model single-variable environmental conditions, models of maternal disease were evaluated for patterns of developmental impairment. While hyperthermia had limited effects on renal development, fetal iron deficiency was associated with severe impairment of renal growth and nephrogenesis with an all-proximal phenotype. Culturing kidney explants under high glucose conditions led to cellular and transcriptomic changes resembling human diabetic nephropathy. Short-term high glucose culture conditions were sufficient for long-term alterations in DNA methylation-associated epigenetic memory. Finally, the role of epigenetic modifiers in renal development was tested using a small compound library. Among the selected epigenetic inhibitors, various compounds elicited an effect on renal growth, such as HDAC (entinostat, TH39), histone demethylase (deferasirox, deferoxamine) and histone methyltransferase (cyproheptadine) inhibitors. Thus, metanephric organ cultures provide a valuable system for studying metabolic conditions and a tool for screening for epigenetic modifiers in renal development.",
keywords = "Animals, DNA Methylation, Diabetic Nephropathies/genetics, Environment, Epigenesis, Genetic, Female, Glucose/toxicity, Humans, Iron/deficiency, Kidney/drug effects, Mice, Organ Culture Techniques/methods, Pregnancy, Prenatal Exposure Delayed Effects/genetics, Transcriptome",
author = "Lars Fuhrmann and Saskia Lindner and Alexander-Thomas Hauser and Clemens H{\"o}se and Oliver Kretz and Cohen, {Clemens D} and Lindenmeyer, {Maja T} and Wolfgang Sippl and Manfred Jung and Huber, {Tobias B} and Nicola Wanner",
year = "2021",
month = apr,
day = "16",
doi = "10.3390/ijms22084157",
language = "English",
volume = "22",
journal = "INT J MOL SCI",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "8",

}

RIS

TY - JOUR

T1 - Effects of Environmental Conditions on Nephron Number: Modeling Maternal Disease and Epigenetic Regulation in Renal Development

AU - Fuhrmann, Lars

AU - Lindner, Saskia

AU - Hauser, Alexander-Thomas

AU - Höse, Clemens

AU - Kretz, Oliver

AU - Cohen, Clemens D

AU - Lindenmeyer, Maja T

AU - Sippl, Wolfgang

AU - Jung, Manfred

AU - Huber, Tobias B

AU - Wanner, Nicola

PY - 2021/4/16

Y1 - 2021/4/16

N2 - A growing body of evidence suggests that low nephron numbers at birth can increase the risk of chronic kidney disease or hypertension later in life. Environmental stressors, such as maternal malnutrition, medication and smoking, can influence renal size at birth. Using metanephric organ cultures to model single-variable environmental conditions, models of maternal disease were evaluated for patterns of developmental impairment. While hyperthermia had limited effects on renal development, fetal iron deficiency was associated with severe impairment of renal growth and nephrogenesis with an all-proximal phenotype. Culturing kidney explants under high glucose conditions led to cellular and transcriptomic changes resembling human diabetic nephropathy. Short-term high glucose culture conditions were sufficient for long-term alterations in DNA methylation-associated epigenetic memory. Finally, the role of epigenetic modifiers in renal development was tested using a small compound library. Among the selected epigenetic inhibitors, various compounds elicited an effect on renal growth, such as HDAC (entinostat, TH39), histone demethylase (deferasirox, deferoxamine) and histone methyltransferase (cyproheptadine) inhibitors. Thus, metanephric organ cultures provide a valuable system for studying metabolic conditions and a tool for screening for epigenetic modifiers in renal development.

AB - A growing body of evidence suggests that low nephron numbers at birth can increase the risk of chronic kidney disease or hypertension later in life. Environmental stressors, such as maternal malnutrition, medication and smoking, can influence renal size at birth. Using metanephric organ cultures to model single-variable environmental conditions, models of maternal disease were evaluated for patterns of developmental impairment. While hyperthermia had limited effects on renal development, fetal iron deficiency was associated with severe impairment of renal growth and nephrogenesis with an all-proximal phenotype. Culturing kidney explants under high glucose conditions led to cellular and transcriptomic changes resembling human diabetic nephropathy. Short-term high glucose culture conditions were sufficient for long-term alterations in DNA methylation-associated epigenetic memory. Finally, the role of epigenetic modifiers in renal development was tested using a small compound library. Among the selected epigenetic inhibitors, various compounds elicited an effect on renal growth, such as HDAC (entinostat, TH39), histone demethylase (deferasirox, deferoxamine) and histone methyltransferase (cyproheptadine) inhibitors. Thus, metanephric organ cultures provide a valuable system for studying metabolic conditions and a tool for screening for epigenetic modifiers in renal development.

KW - Animals

KW - DNA Methylation

KW - Diabetic Nephropathies/genetics

KW - Environment

KW - Epigenesis, Genetic

KW - Female

KW - Glucose/toxicity

KW - Humans

KW - Iron/deficiency

KW - Kidney/drug effects

KW - Mice

KW - Organ Culture Techniques/methods

KW - Pregnancy

KW - Prenatal Exposure Delayed Effects/genetics

KW - Transcriptome

U2 - 10.3390/ijms22084157

DO - 10.3390/ijms22084157

M3 - SCORING: Journal article

C2 - 33923831

VL - 22

JO - INT J MOL SCI

JF - INT J MOL SCI

SN - 1661-6596

IS - 8

M1 - 4157

ER -