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1000 Titel
  • Altered molecular signatures during kidney development after intrauterine growth restriction of different origins
1000 Autor/in
  1. Nüsken, Eva |
  2. Fink, Gregor |
  3. Lechner, Felix |
  4. Voggel, Jenny |
  5. Wohlfarth, Maria |
  6. Sprenger, Lisa |
  7. Mehdiani, Nava |
  8. Weber, Lutz T. |
  9. Liebau, Max Christoph |
  10. Brachvogel, Bent |
  11. Dötsch, Jörg |
  12. Nüsken, Kai |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-02-01
1000 Erschienen in
1000 Quellenangabe
  • 98(3):395-407
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00109-020-01875-1 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080693/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • 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.
1000 Sacherschließung
lokal Developmental kidney programming
lokal Kidney/metabolism [MeSH]
lokal Inflammation
lokal Kidney/growth
lokal Animals [MeSH]
lokal Low protein diet
lokal Rats, Wistar [MeSH]
lokal Original Article
lokal Lipid metabolism
lokal Organ Size [MeSH]
lokal Male [MeSH]
lokal Uterine vessel ligation
lokal Transcriptome [MeSH]
lokal Animals, Newborn [MeSH]
lokal Fetal Growth Retardation/genetics [MeSH]
lokal Intrauterine growth restriction (IUGR)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-0674-804X|https://orcid.org/0000-0001-7042-1706|https://frl.publisso.de/adhoc/uri/TGVjaG5lciwgRmVsaXg=|https://orcid.org/0000-0001-9120-2203|https://frl.publisso.de/adhoc/uri/V29obGZhcnRoLCBNYXJpYQ==|https://frl.publisso.de/adhoc/uri/U3ByZW5nZXIsIExpc2E=|https://frl.publisso.de/adhoc/uri/TWVoZGlhbmksIE5hdmE=|https://frl.publisso.de/adhoc/uri/V2ViZXIsIEx1dHogVC4=|https://frl.publisso.de/adhoc/uri/TGllYmF1LCBNYXggQ2hyaXN0b3Bo|https://frl.publisso.de/adhoc/uri/QnJhY2h2b2dlbCwgQmVudA==|https://frl.publisso.de/adhoc/uri/RMO2dHNjaCwgSsO2cmc=|https://orcid.org/0000-0001-5749-7183
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1000 Erstellt am 2023-04-25T17:35:09.907+0200
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