Popper, Bastian; Rammer, Marian Theodor; Gasparitsch, Mojca; Singer, Teresa; Keller, Ursula; Döring, Yvonne; Lange-Sperandio, Bärbel (2019). Neonatal obstructive nephropathy induces necroptosis and necroinflammation. Scientific reports, 9(1), p. 18600. Springer Nature 10.1038/s41598-019-55079-w
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Urinary tract obstruction during kidney development causes tubular apoptosis, tubular necrosis, and interstitial inflammation. Necroptosis is a subtype of programmed necrosis mediated by the receptor-interacting serine/threonine-protein kinase-3 (RIPK3) and the pseudokinase mixed lineage kinase domain-like (MLKL). Necrosis induces inflammation and stimulates cell death in an autoamplification loop named necroinflammation. Here, we studied necroptosis and necroinflammation in obstructive nephropathy induced by unilateral ureteral obstruction (UUO) in neonatal C57Bl/6J mice. Ureteral obstruction induced tubular dilatation, tubular basement membrane thickening, cast formation, and increased expression of kidney injury molecule-1 (KIM-1). Morphological investigations showed either apoptotic or necrotic cells in the tubular compartment. Biochemical analysis revealed increased caspase-8 activity and upregulation of RIPK3 as well as phosphorylated-MLKL in UUO-kidneys. Pro-inflammatory cytokines (IL-1α, INF-γ, TNF-α) were upregulated following UUO. Taken together we show that necroptosis and necroinflammation are accompanied phenomena in neonatal kidneys with obstruction. These findings may help to develop novel strategies to treat congenital obstructive nephropathy.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Angiology |
UniBE Contributor: |
Döring, Yvonne |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2045-2322 |
Publisher: |
Springer Nature |
Language: |
English |
Submitter: |
Isabel Lorenz |
Date Deposited: |
23 Jan 2020 12:38 |
Last Modified: |
05 Dec 2022 15:35 |
Publisher DOI: |
10.1038/s41598-019-55079-w |
PubMed ID: |
31819111 |
BORIS DOI: |
10.7892/boris.138058 |
URI: |
https://boris.unibe.ch/id/eprint/138058 |
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