Peptide Mimicking Loop II of the Human Epithelial Protein SLURP-2 Enhances the Viability and Migration of Skin...

The secreted human protein SLURP-2 is a regulator of epithelial homeostasis, which enhances the viability and migration of keratinocytes. The targets of SLURP-2 in keratinocytes are nicotinic and muscarinic acetylcholine receptors. This work is devoted to the search for the SLURP-2 functional regions responsible for enhancing keratinocyte viability and migration. We produced synthetic peptides corresponding to the SLURP-2 loop regions and studied their effect on the viability and migration of HaCaT skin keratinocytes using the WST-8 test and scratch-test, respectively. The highest activity was exhibited by a loop II-mimicking peptide that enhanced the viability of keratinocytes and stimulated their migration. The peptide activity was mediated by interactions with α7- and α3β2-nAChRs and suppression of the p38 MAPK intracellular signaling pathway. Thus, we obtained new data that explain the mechanisms underlying SLURP-2 regulatory activity and indicate the promise of further research into loop II-mimicking peptides as prototypes of wound healing drugs.