Project 02

Extracellular proteolysis after surgical trauma of the intestine

Study group Brix
Jacobs University Bremen  l  School of Engineering and Science
Campus Ring 6  l  28759 Bremen

Our project on the regeneration of the intestine after trauma aims to determine whether cysteine proteinases might contribute to the initial phases in the onset of a potentially life-threatening immobility of the gut, which is a common complication after surgery.

As a result of trauma, the non-physiological release of lysosomal enzymes like the cysteine proteinases from damaged cells into the extracellular space could be envisioned. The release of lysosomal enzymes might have dramatic consequences, because of the enzyme’s broad spectrum of potential substrates. Extracellularly occurring lysosomal enzymes would be suspect of damaging neighboring, previously non-damaged cells or constituents of the extracellular matrix. We will focus on the quantitation of the proteolytic potential of intestinal epithelial cells before and after surgery. Because proteolysis is irreversible, special emphasis will be given on the identification of potential substrates of cysteine proteinases during the initial inflammatory phase. As indicators of extracellular proteolysis, the possible degradation of cell surface proteins or of extracellular matrix constituents such as collagens will be analysed.

The regulation of the expression of the lysosomal cysteine proteinases, their transport and secretion in damaged epithelia, and their possible re-internalisation for regeneration will be investigated. A long-term goal of this project is to establish a transgenic mouse model with an intestine-specific expression of cysteine proteinase-green fluorescent protein (GFP) chimeras that would allow to directly track the release and transport pathways after traumatic injury.

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