Expression of platelet-derived growth factor B-chain and platelet-derived growth factor beta-receptor in fibroblasts...

Scleroderma is a fibrotic disease occurring in a localized or systemic form. The pathogenesis of scleroderma remains poorly understood. Recent studies revealed that various cytokines and growth factors were involved in the development of scleroderma fibrosis. Platelet-derived growth factor (PDGF) is a potent growth factor for mesenchymal cells, especially fibroblasts. It can promote fibroblasts proliferation, enhance extracellular matrix synthesis. It is also a chemoattractant to fibroblasts. To better understand the role of PDGF in pathogenesis of scleroderma, we performed both in vivo studies on the expression of PDGF beta-receptor protein in scleroderma tissue and in vitro studies on the expression of PDGF B-chain and PDGF beta-receptor mRNA in cultured fibroblasts derived from both lesions of scleroderma and normal skin. Immunohistochemistry staining showed that PDGF beta-receptor expression was greatly elevated in the dermis of scleroderma lesion whereas PDGF beta-receptor were expressed at low levels in normal skin. Northern blot analysis showed that cultured fibroblasts from scleroderma had higher expression of PDGF B-chain and PDGF beta-receptor mRNA than those from normal control. Two PDGF B-chain mRNA transcripts, 2.8 and 4.0 kb, were expressed. The 2.8 kb transcripts which had more efficient translation ability was the more predominantly expressed one. These results indicate that PDGF B-chain/PDGF beta-receptor signal pathway might be involved in the development of fibrosis in scleroderma, and that the 2.8 kb PDGF B-chain mRNA transcript may be the main modulation gene.