Mutation or deletion of this AP-1 DNA-binding site results in complete loss of induction of CCN1 promoter activity in response to UV irradiation (Quan et al
Mutation or deletion of this AP-1 DNA-binding site results in complete loss of induction of CCN1 promoter activity in response to UV irradiation (Quan et al. in increased CCN1 promoter activity. Treatment with retinoic acid, a CCN1 inhibitor, inhibited UV-induced CCN1 promoter activity. Subsequent use of this assay system to screen anti-aging ingredients revealed that CCN1-GFs treated with sclareol showed decreased levels of UVB-induced CCN1 expression. Sclareol attenuated UVB-induced photo-aging by an increase in collagen synthesis and decrease in MMP-1 activity. and em Salvia officinalis /em YHO-13177 . It is classified as a bicyclic diterpene alcohol and is an amber-colored solid with a sweet, balsamic scent. Sclareol is used as a fragrance in cosmetics and perfumes and as flavoring in food. Interestingly, sclareol treatment down-regulated UVB-induced CCN1. The mechanisms by which sclareol regulates CCN1 promoter activity are unknown. The CCN1 promoter contains a perfect consensus AP-1 site, TGACTCA. Mutation or deletion of this AP-1 DNA-binding site results in complete loss of induction of CCN1 promoter activity in response to UV irradiation (Quan et al. 2010). Additionally, CCN1 expression is regulated via an Egf-1-dependent mechanism after cigarette-smoke-extract exposure in fibroblasts (Kim et al. 2011). It is likely that sclareol reduces CCN1 by inhibition of the AP-1 transcription factor. CCN1 is transcriptionally activated by a variety of extracellular stimuli. Transcriptional regulation of CCN1 in response to UV irradiation is primarily controlled by the AP-1 transcription factor in primary human dermal fibroblasts (Orfanos et al. 1997). AP-1 transcriptional activity is elevated in both chronologically aged and photo-aged human skin, and is critically important in mediating skin connective tissue damage. Elevated AP-1 is suppressed by sclareol in photo-aged human skin in vivo Rabbit Polyclonal to CDC7 (Varani et al. 2000; Fisher et al. 2000; Wang et al. 1999; Fisher et al. 1998), suggesting that sclareol down-regulates CCN1 expression by inhibiting AP-1. Interestingly, elevated CCN1 also activates AP-1 (Quan et al. 2006), suggestive of a positive feedback mechanism in the sustained elevation of CCN1 in aged and photo-aged human skin. Our data suggest that such interactions may be involved in sclareol-mediated regulation of CCN1 expression in fibroblasts, which appears to be a useful model to investigate the nature of these interactions. In conclusion, we presented a YHO-13177 novel and high-throughput screening using NIH3T3 fibroblast cells transfected with AcGFP1-1-CCN1 promoter plasmid. The data acquired in YHO-13177 this study demonstrate the ability of sclareol to suppress photo-aging. Conclusion The CCN1-GFs cell line is a useful tool for the screening of inhibitors of CCN1 expression induced by UVB irradiation. Sclareol, which was selected as a suppressor of CCN1 expression by a cell-based system that utilizes a pAcGFP1-1-CCN1 promoter, suppressed UVB-induced photo-aging. Acknowledgments This research was supported by a grant (A004600326) from Jeju Economic Region Diagram Industry YHO-13177 R&D project Program funded by Jeju Province..