Analysis of the mechanisms of chronification in a sepsis model in a cell- or organ-specific smad2 K.O. mouse

Acronym: SMAD2

Principal Investigator: Dr. rer. nat. Elke Kunisch 

Team: Prof. Dr. med. Raimund W. Kinne

research Area: D Sepsis related Organ Failure

Project Number: D1.4

Duration: 01.08.2010 - 31.07.2012

Module: Rotational Position

The Problem

Currently, nearly nothing is known about organ failure as long-term sequelae of sepsis. The project aims at characterizing the molecular mechanisms of long-term sequelae in a mouse model of sepsis.

Results obtained during the funding period

In collaboration with the CSCC, the Department of Anestesiology and the Institute of Pathology (Jena University Hospital), a long-term murine model of sepsis has been described by our group. The model showed a survival rate of approx. 40%. Whereas clinical severity score, food-intake, and body weight normalized until day 6, 4-week survivors still had an elevated white blood cell and platelet count, as well as elevated levels of markers for liver injury. In the liver of the mice, inflammatory infiltrates and substantial fibrosis was observed. Increased numbers of potentially pathogenetic macrophages and α-SMA-positive cells were detected in the vicinity of fibrotic areas. Together with augmented TGF-ß mRNA expression, increased phosphorylation of its signalling molecule Smad2 was seen. In order to address the role of the pro-fibrotic TGF-ß signalling for organ-fibrosis in sepsis, a fibroblast-specific Smad2 k.o. mouse was established. Initial short-time sepsis trials showed a higher survival rate in fibroblast-specific Smad2 k.o. mice (100%) than in wild-type mice 24 h after sepsis-induction (63%).

Publications

Gonnert FA, Kunisch E, Gajda M, Lambeck S, Weber M, Claus RA, Bauer M, Kinne RW: Hepatic Fibrosis in a Long-Term Murine Model of Sepsis. Shock 2012 Apr, 37(4):399-407

Contact 

Prof. Dr. med. Raimund W. Kinne

Tel.: +49 (0)36691 - 81 228

Universitätsklinikum Jena
Lehrstuhl für Orthopädie
AG Experimentelle Rheumatologie
Klosterlausnitzer Str. 81
07607 Eisenberg