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Open AccessArticle

The Acute Phase Response Is a Prominent Renal Proteome Change in Sepsis in Mice

1
Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary
2
Institute for Translational Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
3
Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, 1000 Ljubljana, Slovenia
4
Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, 1000 Ljubljana, Slovenia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(1), 200; https://doi.org/10.3390/ijms21010200
Received: 18 November 2019 / Revised: 16 December 2019 / Accepted: 20 December 2019 / Published: 27 December 2019
(This article belongs to the Special Issue Inflammation and Oxidative Stress in Kidney Disease)
(1) Background: Sepsis-induced acute kidney injury (AKI) is the most common form of acute kidney injury (AKI). We studied the temporal profile of the sepsis-induced renal proteome changes. (2) Methods: Male mice were injected intraperitoneally with bacterial lipopolysaccharide (LPS) or saline (control). Renal proteome was studied by LC-MS/MS (ProteomeXchange: PXD014664) at the early phase (EP, 1.5 and 6 h after 40 mg/kg LPS) and the late phase (LP, 24 and 48 h after 10 mg/kg LPS) of LPS-induced AKI. Renal mRNA expression of acute phase proteins (APP) was assessed by qPCR. (3) Results: Renal proteome change was milder in EP vs. LP. APPs dominated the proteome in LP (proteins upregulated at least 4-fold (APPs/all): EP, 1.5 h: 0/10, 6 h: 1/10; LP, 24 h: 22/47, 48 h: 17/44). Lipocalin-2, complement C3, fibrinogen, haptoglobin and hemopexin were the most upregulated APPs. Renal mRNA expression preceded the APP changes with peak effects at 24 h, and indicated renal production of the majority of APPs. (4) Conclusions: Gene expression analysis revealed local production of APPs that commenced a few hours post injection and peaked at 24 h. This is the first demonstration of a massive, complex and coordinated acute phase response of the kidney involving several proteins not identified previously. View Full-Text
Keywords: acute kidney injury (AKI); lipopolysaccharide (LPS); renal acute phase reaction (APR); acute phase proteins (APP); mouse acute kidney injury (AKI); lipopolysaccharide (LPS); renal acute phase reaction (APR); acute phase proteins (APP); mouse
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Róka, B.; Tod, P.; Kaucsár, T.; Vizovišek, M.; Vidmar, R.; Turk, B.; Fonović, M.; Szénási, G.; Hamar, P. The Acute Phase Response Is a Prominent Renal Proteome Change in Sepsis in Mice. Int. J. Mol. Sci. 2020, 21, 200.

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