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Involvement of a forkhead transcription factor, FOXO1A, in UV-induced changes of collagen metabolism
Hiroshi Tanaka1, Yuhko Murakami, Izumi Ishii
1Research Laboratories, Nippon Menard Cosmetic Co. Ltd, Nagoya, Japan. tanaka.hiroshi@menard.co.jp
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.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 60-62; doi:10.1038/jidsymp.2009.2.
Insights
Forkhead box O (FOXO) transcription factors are vital for aging. This study reveals FOXO1a regulates collagen and MMPs in skin cells after UV exposure, suggesting a role in skin aging.
Area of Science:
- Molecular Biology
- Dermatology
- Aging Research
Background:
- Forkhead box O (FOXO) transcription factors are key regulators in aging pathways, suppressing detrimental effects of insulin/IGF-1 signaling.
- The role of FOXOs in UV-induced collagen metabolism in dermal fibroblasts remains unexplored.
Purpose of the Study:
- To investigate UV-induced changes in FOXO1a expression in human dermal fibroblasts.
- To determine the role of FOXO1a in regulating collagen synthesis and matrix metalloproteinase (MMP) expression following UV irradiation.
Main Methods:
- Human dermal fibroblasts were exposed to UVA or UVB radiation.
- FOXO1a expression was manipulated using small interfering RNA (siRNA) and peptide treatments.
- Collagen type I (COLIAI) and MMP-1, MMP-2 mRNA levels were quantified.
Main Results:
- UV irradiation significantly decreased FOXO1A mRNA levels, type I collagen (COLIAI) expression, and increased MMP-1 and MMP-2 mRNA levels.
- FOXO1a knockdown via siRNA mimicked UV-induced changes, decreasing COLIAI and increasing MMPs.
- FOXO1a peptide treatment reversed these effects, indicating its regulatory role.
Conclusions:
- FOXO1a is implicated in the regulation of type I collagen and MMP expression in dermal fibroblasts subjected to UV stress.
- These findings suggest FOXO1a may play a significant role in skin aging processes influenced by UV radiation.
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