PhD Scientific Days 2020

Theoretical and Translational II. Posters

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

Előadó neve

Róka, Beáta

Előadó munkahelye

Institute of Translational Medicine

Előadó telefonszáma

+36304713562

Előadó e-mail címe

beata.roka@gmail.com

Az előadás címe

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

Szerző(k) neve és munkahelye

Beáta Róka1, Pál Tod1,2, Tamás Kaucsár1, Matej Vizovišek3, Robert Vidmar3, Boris Turk3,4, Marko Fonović3,4, Gábor Szénási1 and Péter Hamar1,2
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

Szekció

Theoretical and Translational II. Posters

Language of the presentation

English

Section, first choice

Molecular Sciences

Section, second choice

Theoretical and Translational Medicine

Összefoglaló szövege

Introduction: Septic acute kidney injury (AKI) is the most common form of AKI with poor outcomes. Intraperitoneal (i.p.) injection of bacterial lipopolysaccharide (LPS) is used to model systemic inflammation during sepsis.
Aim: Our aim was to study the temporal profile of the renal proteome changes in LPS-induced AKI.
Methods: Male mice were injected i.p. with LPS or saline (control). AKI was assessed by measuring plasma urea concentration and renal mRNA expression of TNFα, IL-6 and neutrophil gelatinase-associated lipocalin (Lcn-2). 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.
Results: AKI was indicated by increased renal TNFα, IL-6 and Lcn-2 mRNA expression from 1.5 h after LPS administration. Plasma urea concentration was elevated from 6 h and started to decline at 48 h. Renal proteome change was milder in EP than in LP. APPs dominated the proteome changes in LP. The ratio of APPs among all the proteins upregulated at least 4-fold were as follows (APPs/all): EP, 1.5h: 0/10, 6h: 1/10; LP, 24h: 22/47, 48h: 17/44. Lipocalin-2, complement C3, fibrinogen, haptoglobin and hemopexin were the most upregulated APPs. Renal mRNA expression preceded the APP concentration changes with peak effects at 24 h. LPS upregulated renal ceruloplasmin and haptoglobin mRNA expression from 1.5 h, and fibrinogen-α, -β, -γ, serum amyloid A, hemopexin, ferritin heavy chain and inter alpha-trypsin inhibitor 4 mRNA from 6 h. Complement C3 and transferrin mRNA were upregulated only in LP. Albumin mRNA was downregulated in LP.
Conclusions: Gene expression analysis revealed local production of the majority 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.

Additional Information

Supervisors:
Péter Hamar, e-mail address: hamar.peter@med.semmelweis-univ.hu
Gábor Szénási, e-mail address: szenasi.gabor@med.semmelweis-univ.hu

Bemutatás módja

Poszter

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4723

Start

12:53

End

12:56

Authors (legacy)

Beáta Róka1, Pál Tod1,2, Tamás Kaucsár1, Matej Vizovišek3, Robert Vidmar3, Boris Turk3,4, Marko Fonović3,4, Gábor Szénási1 and Péter Hamar1,2
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