Untersuchungen zu der Rolle von MORG1 und HIF-1α in der Sepsis induzierten Nierenschädigung / Claudia Schindler

Sepsis is a generalized hyperinflammatoric host response caused by infection. Renal dysfunction is frequently associated with sepsis due to limited supply of tissue oxygen in renal tissue, and extremely strong host immune response. Hypoxia inducible factor1 and 2 alpha (HIF1/2α) are essential for cellular adaptation to hypoxic conditions. Under normoxia, the regulation of HIF1α occurs by prolylhydroxylases (PHDs) via proteasomal degradation. The scaffold protein MAPK organizer 1 (MORG1) interacts with PHD3 and provides the regulation and stabilization of HIF1/2α proteins. The role of MORG1 in relation to enhanced HIF1α protein levels in sepsisinduced renal injury has not yet been investigated. Therefore, in this study we have analysed the influence of sepsis dependent kidney damage in Morg1+/- and wildtype mice. Peritonitis was induced in cecal ligation and punction (CLP) and peritoneal contamination and infection (PCI), in addition endotoxemia was studied in lipopolysaccharides (LPS) treated mice. To figure out impact of MORG1PHD3HIF complex in sepsisinduced renal injury kidney morphology, function, and inflammatory markers were explored as well as survival studies were performed. HIF1/2α was accumulated in renal tissue after sepsis induction. The reduction of MORG1 or/and stabilization of HIF1/2α protein showed renoprotective effects in kidney of Morg1+/- animals, demonstrated as less vacuolization, tubular apoptosis, and necrosis after sepsis or LPS. In agreement with these observations, Morg1+/- mice were protected against infiltration of CD3+Tcells. However, that did not reflect systemic inflammation, as we did not detect significant differences in inflammatory cytokine concentrations in blood plasma. Furthermore, renal function was deteriorated due to sepsis and endotoxemia in both genotypes to similar extend. Furthermore, our survival data have shown that suppression of MORG1 expression was correlated with increased lethality of septic animals.

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Person: Schindler, Claudia [Author]
Corporate Author: Friedrich-Schiller-Universität Jena [Degree granting institution]
Format: Book
Language(s):German
Publication:Jena, 2015
Printing place:Jena
Dissertation:Jena, Univ., Diss., 2015
Subjects:Sepsis > Nierenfunktionsstörung > Pathogenese
Type of content:Hochschulschrift
Related resources:Erscheint auch als Online-Ausgabe: Untersuchungen zu der Rolle von MORG1 und HIF-1α in der Sepsis induzierten Nierenschädigung
Physical description:93, XII Bl. : Ill., graph. Darst. ; 30 cm
Basic Classification: 44.75 Infektionskrankheiten, parasitäre Krankheiten