Involvement of a forkhead transcription factor, FOXO1a, in UV-induced changes of collagen metabolism

Abstract

Transcription factors belonging to the forkhead box gene, group O (FOXOs) family have been found to be crucial in downstream suppression of life-shortening effects of the insulin/insulin-like growth factor-1 (IGF-1) signaling pathway, which accelerates aging by suppressing FOXOs. Thus, FOXOs could hold the key for counteracting aging. Although FOXOs may play a critical role in aging, the effects of FOXOs on UV-induced changes of collagen metabolism by dermal fibroblasts are unknown. In this study, UV-induced changes in FOXO1a expression and the roles of FOXO1a in the regulation of collagen synthesis and matrix metalloproteinase (MMPs) expression in human dermal fibroblasts were investigated. In UVA- or UVB-irradiated fibroblasts, the expression of FOXO1A mRNA decreased significantly. The expression of type I collagen (COLIAI) also decreased. On the other hand, MMP-1 and MMP-2 mRNA levels increased. FOXO1A-small interfering RNA transfection induced the downregulation of FOXO1A expression, it also induced a decrease in COLIAI expression, and it increased MMP-1 and MMP-2 expression. These changes are similar to those observed in UV-irradiated fibroblasts. Furthermore, FOXO1a-peptide induced opposite changes in COLIAI, MMP-1, and MMP-2 expression. Therefore, FOXO1a is involved in the UV-induced changes of type I collagen and MMPs expression. © 2009 The Society for Investigative Dermatology.