SKIN CARE 39 40%


n Not treated n Placebo n 0.025% shMmw n 0.025% Signal-10


30%


20%


10%


0%


-10% T0,5 T1 T2 Time (hours) Figure 2: In vivo study: on 10 women, age 18 to 65. Material: Corneometer®


cases, it therefore becomes very important not only to characterise the chemical nature of the active ingredient, but also its real efficacy. Skins are as different as molecular


weights are. They react in specific, varied ways, but are all based on the same pool of native ingredients, among which are the dominant hyaluronans. Just like our skin, the physiology of this polymer varies with its environment, essentially due to its molecular weight. Recent studies have showed the stimulative influence of a LMW HA in stress conditions as opposed to the calming influence of a HMW in homeostatic phase.1,2


The capacity to


deliver a specific spectrum of molecular weight instead of a common single peak consequently makes biological sense if considering the possible synergies between the different molecules.


CD44 receptor characteristics CD44 is a transmembrane glycoprotein encoded by a single gene and expressed as several isoforms, due to intensive alternative RNA splicing (insertion of up to 11 additional exons into a site within the membrane-proximal portion of the 248 amino-acids extracellular domain), and differential post-translational modifications such as glycosylation or the attachment of glycosaminoglycans. However, the HA binding site is present on all isoforms, and our focus will be on the predominant


September 2020 . Skin moisturisation is measured at T0.5, T1, T2, T4, T8 and T24 after single


cream application. Moisturisation is measured on not treated area, placebo cream area, 0,25% medium mw sodium hyaluronate cream area, and 0,25% SIGNAL-10 cream area.


standard form. Many studies have been led on the


interactions between receptor CD44 and its ligand, as it is a convergence point for many mechanisms in the physiology of important cells, including skin cells such as keratinocytes or fibroblasts. The capacity of HA to directly modify cell behaviour had already been understood since 1980, when two demonstrations showed specific binding with intact cells2,3


and the


enhancement of cell motility in two- dimensional cultures.4


Later studies


showed that the ability of HA to activate intracellular signalling cascades required interactions with hyaladherins, but was additionally modified by the amount and size of HA present in the environment of the cells.2 This trend of perception has been


expanding lately, admitting that it becomes increasingly evident that mesenchymal cells (such as fibroblasts) are provided with the capacity to sense changes in their local environment (a volume in which the cells are evolving), especially when homeostasis is compromised. In this case, cell surface receptors are first exposed to detect even subtle changes in the local tissue environment, and can lead to the first cellular answers to re-establish homeostasis or tissue integrity. Hyaluronan signalling involving CD44 is in this case coupled with downstream pathways that


can consequently be greatly influenced by the size of external hyaluronan constituting the cell background.


CD44 / hyaluronan interactions The smallest hyaluronan fragment binding to a CD44 is a hexasaccharide,5


and the


latest studies evaluated in vitro that HA with a molecular weight up to 10kDa could bind reversibly to its specific receptor, whereas the binding capacity of HA with a molecular weight superior to 30kDa could be regarded as irreversible6


as it probably


binds to many CD44 at the same time. However, this binding affinity (regulating ligand/receptor interaction) is itself regulated by the expression of CD44. In fact, CD44 functionality seems to depend on the cellular context (in activation/deactivation mechanism). However, in the case of cells such as fibroblasts, they are constitutively active, always in the “ON” position, but appear to leave much more subtlety in the possibilities of influencing fibroblast physiology. New scientific opinions describe the


difference of physiochemical properties of LMW HA versus HMW HA and the consequent adverse cell reaction due to a distinct interaction with CD44. When skin integrity is compromised (wound, oxidation), an ensemble of reactions tends to cut HMW HA into fragments, considered “danger” signals.7


Invading PERSONAL CARE EUROPE T4 T8 T24


Moisturization (in vivo)


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