Effect of the abrogation of TGF-β1 by antisense oligonucleotides on the expression of TGF-β-isoforms and their receptors I and II in isolated fibroblasts from keloid scars
Disequilibrium of dermal wound repair can result in continued accumulation of ECM and excessive scar formation. In susceptible genetically predisposed individuals, keloid formation can be observed. Keloid disease represents a benign dermal fibroproliferative tumor that is unique to humans. TGF-β is...
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Published in | International journal of molecular medicine Vol. 25; no. 6; pp. 915 - 921 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
D.A. Spandidos
01.06.2010
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Online Access | Get full text |
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Summary: | Disequilibrium of dermal wound repair can result in continued accumulation
of ECM and excessive scar formation. In susceptible genetically predisposed individuals,
keloid formation can be observed. Keloid disease represents a benign dermal fibroproliferative
tumor that is unique to humans. TGF-β is known to play a key role in the pathogenesis
of this disease which is still not fully understood. The isoforms TGF-β1 and TGF-β2
have profibrotic properties, whereas TGF-β3 may have antifibrotic functions. TGF-β
exerts its influence by binding to type I and type II TGF-β receptors, thereby
forming a complex and activating specific downstream effector molecules. The aim
of this study was to investigate the effect of TGF-β1 targeting by antisense oligonucleotides
on the RNA synthesis and protein expression of TGF-β isoforms and their receptors
in keloid-derived fibroblasts. In tissue samples with normal fibroblasts (NFs)
serving as control samples, expression of TGF-β1 and -β2 was decreased when compared
to keloid fibroblasts (KFs), while expression of TGF-β3 and of TGF-βRII was significantly
higher in NFs. In the ELISA assay, abrogation of TGF-β1 led to a significant decrease
in TGF-β1 and -β2 (p<0.05). Expression of TGF-β2 mRNA was reduced. Expression
of TGF-β3 mRNA revealed contrary patterns in KFs from different patients while
expression of TGF-βRI was found to be equal during the measurement period. TGF-βRII
mRNA expression was increased after 48 and 72 h respectively. There is growing
evidence for a regulatory mechanism between TGF-β1 and its receptors. Our findings
support this theory by suggesting interrelations between the different TGF-β isoforms
and their receptors. Abnormal response of KFs to TGF-βmight reflect a modification
in the regulatory pathway that occurs at the receptor level or during intracellular
trans-duction. Improving the understanding of TGF-β in keloid disease could lead
to the development of clinically useful therapeutic modalities for treatment of
keloid disease or even allow identification of preventive strategies. |
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ISSN: | 1107-3756 1791-244X |
DOI: | 10.3892/ijmm_00000422 |