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