Original Article
Constitutive Phosphorylation of Focal Adhesion Kinase Is Involved in the Myofibroblast Differentiation of Scleroderma Fibroblasts

https://doi.org/10.1111/j.0022-202X.2005.23701.xGet rights and content
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Most of the cultured scleroderma fibroblasts have been reported to be myofibroblasts that have the ability to express α smooth muscle actin (αSMA). It is reported that, in human lung fibroblasts, αSMA is induced by transforming growth factor-β (TGF-β), which requires focal adhesion kinase (FAK) phosphorylation on its Tyr-397 site. In this study, we investigated how αSMA expression is upregulated in cultured scleroderma fibroblasts. 4-amino-5-(4-chlorophenyl)-7-(butyl)pyrazolo[3,4-d]pyrimidine, which is a pharmacologic inhibitor of FAK/Src, markedly diminished upregulated αSMA expression in scleroderma fibroblasts as well as in normal fibroblasts stimulated with TGF-β. Likewise, αSMA expression was significantly reduced in sclerderma fibroblasts transfected with kinase-deficient FAK mutant. FAK phosphorylation levels on Tyr-397 in scleroderma fibroblasts were significantly higher than those in normal fibroblasts. Both αSMA expression and FAK phosphorylation levels in scleroderma fibroblasts were markedly diminished by the treatment with TGF-β antisense oligonucleotide. These results indicate that the constitutive phosphorylation of FAK, which is possibly because of the autocrine TGF-β signaling, may play an important role in αSMA expression in scleroderma fibroblasts.

Keywords

α smooth muscle actin
focal adhesion kinase
scleroderma fibroblasts

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