Involvement of a forkhead transcription factor, FOXO1A, in UV-induced changes of collagen metabolism.
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.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 60-62; doi:10.1038/jidsymp.2009.2.
Tanaka
Hiroshi
H
Research Laboratories, Nippon Menard Cosmetic Co. Ltd, Nagoya, Japan. tanaka.hiroshi@menard.co.jp
Murakami
Yuhko
Y
Ishii
Izumi
I
Nakata
Satoru
S
D001483:Base Sequence; D002460:Cell Line; D003094:Collagen / Q000378:metabolism*; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D017931:DNA Primers / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D017931:DNA Primers; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1