Nuesken, Eva, Fink, Gregor, Lechner, Felix, Voggel, Jenny, Wohlfarth, Maria, Sprenger, Lisa, Mehdiani, Nava, Weber, Lutz T., Liebau, Max Christoph ORCID: 0000-0003-0494-9080, Brachvogel, Bent, Doetsch, Joerg and Nuesken, Kai-Dietrich (2020). Altered molecular signatures during kidney development after intrauterine growth restriction of different origins. J. Mol. Med., 98 (3). S. 395 - 408. HEIDELBERG: SPRINGER HEIDELBERG. ISSN 1432-1440

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Abstract

This study was performed to identify transcriptional alterations in male intrauterine growth restricted (IUGR) rats during and at the end of nephrogenesis in order to generate hypotheses which molecular mechanisms contribute to adverse kidney programming. IUGR was induced by low protein (LP) diet throughout pregnancy, bilateral uterine vessel ligation (LIG), or intrauterine stress (IUS) by sham operation. Offspring of unimpaired dams served as controls. Significant acute kidney damage was ruled out by negative results for proteins indicative of ER-stress, autophagy, apoptosis, or infiltration with macrophages. Renal gene expression was examined by transcriptome microarrays, demonstrating 53 (LP, n = 12; LIG, n = 32; IUS, n = 9) and 134 (LP, n = 10; LIG, n = 41; IUS, n = 83) differentially expressed transcripts on postnatal days (PND) 1 and 7, respectively. Reduced Pilra (all IUGR groups, PND 7), Nupr1 (LP and LIG, PND 7), and Kap (LIG, PND 1) as well as increased Ccl20, S100a8/a9 (LIG, PND 1), Ifna4, and Ltb4r2 (IUS, PND 7) indicated that inflammation-related molecular dysregulation could be a common feature after IUGR of different origins. Network analyses of transcripts and predicted upstream regulators hinted at proinflammatory adaptions mainly in LIG (arachidonic acid-binding, neutrophil aggregation, toll-like-receptor, NF-kappa B, and TNF signaling) and dysregulation of AMPK and PPAR signaling in LP pups. The latter may increase susceptibility towards obesity-associated kidney damage. Western blots of the most prominent predicted upstream regulators confirmed significant dysregulation of RICTOR in LP (PND 7) and LIG pups (PND 1), suggesting that mTOR-related processes could further modulate kidney programming in these groups of IUGR pups. Key messages Inflammation-related transcripts are dysregulated in neonatal IUGR rat kidneys. Upstream analyses indicate renal metabolic dysregulation after low protein diet. RICTOR is dysregulated after low protein diet and uterine vessel ligation.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Nuesken, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fink, GregorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lechner, FelixUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Voggel, JennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wohlfarth, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sprenger, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mehdiani, NavaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, Lutz T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liebau, Max ChristophUNSPECIFIEDorcid.org/0000-0003-0494-9080UNSPECIFIED
Brachvogel, BentUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doetsch, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuesken, Kai-DietrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-347669
DOI: 10.1007/s00109-020-01875-1
Journal or Publication Title: J. Mol. Med.
Volume: 98
Number: 3
Page Range: S. 395 - 408
Date: 2020
Publisher: SPRINGER HEIDELBERG
Place of Publication: HEIDELBERG
ISSN: 1432-1440
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
LOW-BIRTH-WEIGHT; RENIN-ANGIOTENSIN SYSTEM; MATERNAL PROTEIN RESTRICTION; UTERINE ARTERY LIGATION; MESANGIOPROLIFERATIVE GLOMERULONEPHRITIS; UTEROPLACENTAL INSUFFICIENCY; ADULT HYPERTENSION; BLOOD-PRESSURE; RAT; DISEASEMultiple languages
Genetics & Heredity; Medicine, Research & ExperimentalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/34766

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