β-Lapachone Regulates the Transforming Growth Factor-β-Smad Signaling Pathway Associated with Collagen Biosynthesis in Human Dermal Fibroblasts

Abstract

The transforming growth factor (TGF)-beta-Smad signaling pathway regulates collagen biosynthesis in human dermal fibroblasts. We found that g-lapachone stimulated type I collagen expression in human dermal fibroblasts. In this study, we evaluated whether the beta-lapachone-induced upregulation of collagen biosynthesis in human dermal fibroblasts is associated with the TGF-beta-Smad signaling pathway. In cultured human dermal fibroblasts, both Smad 2 and Smad 3 (Smad 2/3) were phosphorylated by beta-lapachone treatment in a concentration-dependent manner. SB431542, a specific inhibitor of TGF-beta receptor I kinase, inhibited the beta-lapachone-mediated Smad 2/3 phosphorylation and type I collagen expression, suggesting that beta-lapachone stimulates collagen production via the TGF-beta receptor I kinase-dependent pathway. beta-Lapachone did not increase TGF-beta synthesis in human dermal fibroblasts, suggesting that the molecular mechanism of beta-lapachone for the upregulation of collagen synthesis is due to the extracellular regulation of availability and activities of TGF-beta. This study provides new insights into the role of beta-lapachone in collagen synthesis in human dermal fibroblasts and suggests that beta-lapachone can be used as a pharmacological tool to study collagen homeostasis associated with TGF-beta-Smad signaling.