Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan

Correspondence: Hironobu Ihn, Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Email: IN-DER@h.u-tokyo.ac.jp

Received 8 November 2004; Revised 27 December 2004; Accepted 3 January 2005.

Abstract

Most of the cultured scleroderma fibroblasts have been reported to be myofibroblasts that have the ability to express smooth muscle actin (SMA). It is reported that, in human lung fibroblasts, SMA is induced by transforming growth factor- (TGF-), which requires focal adhesion kinase (FAK) phosphorylation on its Tyr-397 site. In this study, we investigated how SMA 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 SMA expression in scleroderma fibroblasts as well as in normal fibroblasts stimulated with TGF-. Likewise, SMA 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 SMA expression and FAK phosphorylation levels in scleroderma fibroblasts were markedly diminished by the treatment with TGF- antisense oligonucleotide. These results indicate that the constitutive phosphorylation of FAK, which is possibly because of the autocrine TGF- signaling, may play an important role in SMA expression in scleroderma fibroblasts.