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P21
AUTOCRINE AND PARACRINE REGULATION OF PDGF-A AND PDGF-B GENE
EXPRESSION AND THE
CORRESPONDING PDGF RECEPTOR IN CULTURED DERMAL PAPILLA CELLS
AND FOLLICULAR KERATINOCYTES OF THE
HUMAN HAIR FOLLICLE
Kamp H., Geilen C.C., Orfanos C.E., Blume-Peytavi U.; Department
of Dermatology, University Medical Center Benjamin Franklin,
The Free University of Berlin, Germany
Platelet-derived growth factors (PDGF) are potent mitogens
for dermal fibroblasts and other cell types, able to directly
stimulate proliferation and to indirectly regulate angiogenesis
by influencing VEGF expression. Mitogenic activity is mediated
by two PDGF receptors which dimerize upon binding of PDGF
and exert their further biological activity.
As PDGF have been reported to play in addition an important
role in hair follicle formation we investigated the expression
of the different PDGF isoforms as well as their corresponding
receptors in cultured dermal papilla cells (DPC) and follicular
keratinocytes (FK) of the human hair follicle. Furthermore
we examined the regulation of PDGF by different cytokines
(Il-1b,
TNFa,
TGFb1,
IL-4 and IFNg),
important for hair follicle regulation.
We demonstrated by PCR experiments and Western Blot analysis
that DPC strongly express both types of PDGF receptors, a
and b,
whereas FK only weakly express both receptors at the gene
expression level. Expression of PDGF-A mRNA could be detected
in both, FK and DPC, whereas PDGF-B mRNA could only be detected
with a low expression level in FK. PDGF-A mRNA expression
was downregulated by IL-1b
and IFNg
in DPC as well as in FK; a significant down- regulation
of PDGF-B mRNA occured in FK stimulated by IL-1b.
The present study suggests an autocrine loop for PDGF-A in
DPC and for PDGF-B in FK. As only FK synthesize PDGF-B a paracrine
influence of DPC expressing the PDGF-receptor b
has to be Considered.
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