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Article

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

1
III Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
2
Department of Medicine IV, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
3
Institute of Pharmaceutical Sciences, University of Freiburg, 79104 Freiburg, Germany
4
Nephrological Center, Medical Clinic and Policlinic IV, University of Munich, 80336 Munich, Germany
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Institute of Pharmacy, Martin-Luther-University of Halle-Wittenberg, 06120 Halle (Saale), Germany
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CIBSS—Centre for Integrative Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Giuseppina T. Russo
Int. J. Mol. Sci. 2021, 22(8), 4157; https://doi.org/10.3390/ijms22084157
Received: 23 March 2021 / Revised: 8 April 2021 / Accepted: 15 April 2021 / Published: 16 April 2021
(This article belongs to the Special Issue Novel Aspects in Kidney Disease in Diabetes)
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. View Full-Text
Keywords: renal development; nephron number; diabetic nephropathy; epigenetic regulation; iron deficiency; DNA methylation renal development; nephron number; diabetic nephropathy; epigenetic regulation; iron deficiency; DNA methylation
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MDPI and ACS Style

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. Effects of Environmental Conditions on Nephron Number: Modeling Maternal Disease and Epigenetic Regulation in Renal Development. Int. J. Mol. Sci. 2021, 22, 4157. https://doi.org/10.3390/ijms22084157

AMA Style

Fuhrmann L, Lindner S, Hauser A-T, Höse C, Kretz O, Cohen CD, Lindenmeyer MT, Sippl W, Jung M, Huber TB, Wanner N. Effects of Environmental Conditions on Nephron Number: Modeling Maternal Disease and Epigenetic Regulation in Renal Development. International Journal of Molecular Sciences. 2021; 22(8):4157. https://doi.org/10.3390/ijms22084157

Chicago/Turabian Style

Fuhrmann, Lars, Saskia Lindner, Alexander-Thomas Hauser, Clemens Höse, Oliver Kretz, Clemens D. Cohen, Maja T. Lindenmeyer, Wolfgang Sippl, Manfred Jung, Tobias B. Huber, and Nicola Wanner. 2021. "Effects of Environmental Conditions on Nephron Number: Modeling Maternal Disease and Epigenetic Regulation in Renal Development" International Journal of Molecular Sciences 22, no. 8: 4157. https://doi.org/10.3390/ijms22084157

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