γ-Propoxy-sulfo-lichenin, a semisynthetic polysaccharide of Lichenan shows strong activity in keratinocyte differentiation

γ-Propoxy-sulfo-lichenin (γ-PSL) is a semisynthetic polysaccharide obtained by etherification of lichenan, a β-1,3/1,4-glucan from Cetraria islandica L. and propansulton. Substitution of the glucan with 3-propoxy sulfuric acid was shown by NMR studies predominantly at position O-2.

γ-PSL did not show any signs of toxicity against human kerationcytes up to 100 µg/mL (MTT vitality assay, IC₅₀= 143 µg/mL), but significantly increased keratinocyte differentiation: the typical differentiation-specific proteins cytokeratin 1/10, involucrin and loricrin were upregulated by γ-PSL. This induction of differentiation was much stronger compared to the unsubstituted lichenan [1].

Also on gene level stimulation of cell differentiation was observed. An increased gene expression of Cytokeratin 1/10, involucrin, fillagrin, loricrin and transglutaminase 1 could be proven by time-dependent qPCR up to 60 hours. By use of qPCR screening plates for keratinocyte differentiation signalling (Bio-Rad) γ-PSL was characterized to act via calcium depended signalling pathway towards a changed differentiation process. Cell cycle analysis was not influenced by γ-PSL. Scratch assay over 72h did not indicate a significant influence of γ-PSL (100 µg/mL) on cell migration behaviour.

Summarizing γ-PSL is a strong and specific inductor of keratinocyte differentiation, rationalizing the potential use of this polysaccharide for improved wound healing and specific directed differentiation. γ-PSL is significantly more potent in this indication as unsubstituted lichenan, which is traditionally used for its moderate activity for treatment of irritated skin and epithelia.

[1] D. Zacharski (2014) Lichenan from Cetraria islandica (L.) ACH. and xyloglucan from Tropaeolum majus L. as inductors of cellular differentiation