[Impact of TGF-beta1 antisense on collagen-binding integrins in keloid].
BACKGROUND
The treatment of keloids remains challenging due to sparse knowledge about the pathogenesis of this disease. Transforming growth factor (TGF)-beta1 plays a central role in keloid formation. Cell-matrix communication is controlled by integrins, the expression of which can be regulated by TGF-beta1.


METHODS
Using immunohistochemistry we compared expression patterns of alpha1beta1, alpha2beta1 und alpha3beta1 in normal skin and keloid tissue. Secondly, the effect of TGF-beta1-antisense after 48 h and 72 h incubation in a keloid-derived fibroblast monolayer was analyzed by means of reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry.


RESULTS
alpha1beta1 and alpha2beta1 were highly expressed in keloid fibroblasts. Incubation with TGF-beta1-antisense lead to a reduction on protein level. RT-PCR demonstrated an increase of all alpha subunits, while on an mRNA level a decrease of the subunit beta1 could be observed.


CONCLUSIONS
Integrin expression is directly modulated by TGF-beta1. An abnormal response in the keloid as a result of an altered TGF-beta1 pathway could be a key element to understanding the development of keloids.
Bran
G
G
Universitäts-HNO-Klinik, Universitätsklinikum Mannheim, Universität Heidelberg, Deutschland. gregor.bran@umm.de
Sommer
U
U
Meinzer
F
F
Goessler
U R
UR
Hörmann
K
K
Riedel
F
F
Sadick
H
H
D003094:Collagen / Q000378:metabolism*; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D016023:Integrins / Q000378:metabolism*; D007627:Keloid / Q000473:pathology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
D016023:Integrins; D016376:Oligonucleotides, Antisense; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D003094:Collagen
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