The
research group of Dr. Alexandra Deters deals with the effects of plant
secondary metabolites, especially carbohydrates on human skin cells. In
particular we investigate the underlying mechanism of carbohydrate
activity on
primary human keratinocytes and fibroblasts and
focus on signal transduction within these cells and their intercellular
communication. In first studies we found out that carbohydrates
stimulated or inhibited the proliferation, metabolic activity and
differentiation of keratinocytes and fibroblasts in a different way
dependent on their composition. Lately we approved these former results
by investigations concerning involved signal pathways. One utter potent
carbohydrate is a
xyloglucan from Ispaghula seeds stimulating
the proliferation of keratinocytes. With first investigations of
proliferation specific signal way components like growth factors and
their membranous receptors we observed that the gene expression of
keratinocyte growth factor receptor is up regulated. But this effect
does not explain the strong increase of proliferation rates. In case of
an arabinogalactan that stimulated the proliferation of fibroblasts we
found out that neither
the gene expression of extra cellular receptors were influenced nor
growth factors or
signal transducer and activators of transcription
were responsible. Confocal laser scanning microscopy studies showed
that this arabinogalactan was internalized by endosomes. For the future
we will zoom in on the cellular targets of structurally characterized
xyloglucans and outline the differences between their effects on
keratinocytes and fibroblasts. In the focus of interest are
intra cellular signal pathway proteins
(e.g. protein kinases, signal transducers and activators of
transcription) and nuclear envelope receptors (e.g. PPARs).
Additionally
proteins of the extra cellular matrix, for example
adhesion molecules or matrix metallo proteinases are interesting
targets of xyloglucans. At the present we realize this undertaking with
fluorescence activated flow cytometry, ELISA, confocal laser scanning
microscopy, Real-Time PCR and different colorimetric cell based or
functional assays. The availability of skin cells is warranted via
cultures of cell lines HaCaT (keratinocytes), BUD-8 and WST-1
(fibroblasts) and cooperation with surgery departments of the
University of Muenster. The working group is integrated in a network of
chemical and pharmacological institutes.
