Abstract
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. 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. 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. 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.
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