16 SKIN MICROBIOME
between the skin microbiome and age may exist. In this context, it would be of interest to study the possible link between skin aging (e.g., appearance of wrinkles and spots) and specific microbial signatures in order to assess whether skin aging can be modulated by manipulating the microbiome. In this framework, a more comprehensive appreciation of the factors that drive interindividual skin microbiome variation is needed.
Epigenetic modulation The objective of this study was to evaluate exosome-mediated effects of the sensitive skin cosmetic ingredient on genomic targets involved in different skin pathways. Exosomes are responsible for an intercellular communication through the exchange of regulator factors secreted between neighboring and surrounding cells. Lipids and proteins are the main components of exosome membranes, but they also contain messenger RNAs (mRNAs), microRNAs (miRNAs) and other non-coding RNA (RNAnc), as well as diverse molecules involved in the formation, secretion and trafficking of exosomes.12
The
miRNA property to finely-tune gene expression makes them right for immune system regulation, which requires precise control for proper activity. In this way, through epigenetic mechanisms, exosomes regulate biological activities of close or distant target cells. Given this ability to regulate simultaneously many targets, miRNAs are fundamental regulators in physiological conditions such as in the aging process. We performed a screen on several
genomic targets and micro-RNA. The exosome-based communication was evaluated on the sensitive skin active- stimulated keratinocytes, and keratinocyte exosomes by measuring expression levels of specific miRNA and targets genes by real-time PCR. As results, histograms merging results
from the 3 replicates showed that miR-210 was statistically induced by the sensitive skin cosmetic ingredient stimulated keratinocytes compared to untreated keratinocytes (p<0.05)(Fig 5). These results pointed out the induction
of miR-210 in keratinocytes. This induction is perfectly correlated with the repression of 2 potential miR-210 targets identified by TArbase (miRbase software): HIF1AN (HIF-1) and RHOB. HIF1AN (Hypoxia Inducible Factor 1
Subunit Alpha Inhibitor), a master transcriptional regulator of adaptative response to hypoxia with pivotal role in angiogenesis, is upregulated via inflammatory cytokines. RhoB (Ras Homolog Family Member B) known to regulate cytokines trafficking is
PERSONAL CARE NORTH AMERICA 10
7.5 5
2.5 0
-2.5 -5
-7.5 -10
-12.5 -15
-36% *
Figure 7: Evaluation of TEWL by Tewameter TM 300® Khazaka CM 825 Corneometer® placebo).
also increased in response to inflammatory cytokines, mainly through NF-kB pathway. The downregulation of two genes
playing a key role in the induction and maintenance of inflammation, emphasizes the absence of inflammation in our context. Altogether, the perfect correlation of
miR-210 induction with the repression of miR-210 target genes support the positive regulation of miR-210 via exosomale stimulation resulting in the absence of inflammation. These results highlighted the
+33% *
5
+200% *
2.5 0
-2.5 -5
-7.5 -10
-12.5 -15
-17.5 -129% * n Placebo n Kalmethic® 0.5% a* parameter L* parameter
Figure 6: Evaluation of the anti-redness (a*parameter) & clarity (L*parameter) effect of Kalmethic® Minolta CM700-d Spectrocolorimeter® (* p-value<0.05 vs placebo).
. The statistical analysis was performed using T-test
by
TWEL Cutaneous hydration rate
n Placebo n Kalmethic®
0.5% and the moisturizing effect by Courage & . The statistical analysis was performed using T-test (* p-value<0.05 vs
beneficial role of NF-kB and TLR2 supporting tight junction strengthening and cellular migration & reparation. The positive modulation of TLRs
inducing a positive feedback loop on transcription factor NF-kB which in turn positively activates downstream pathway on epithelization in keratinocytes was confirmed by direct modulation of the sensitive skin cosmetic ingredient on key genomic targets in keratinocytes. Expression levels of CD44, CDH1, CLDN1, DSG1 and FGF7 measured by RT-qPCR
October 2020
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