Human epithelial protein SLURP-2 as a prototype of drugs for wound healing

Wound healing is a complex process based on the regulation of proliferation and migration of epithelial cells. Chronic wounds are characterized by increased proliferation and lack of migration of epidermal cells. The secreted human protein SLURP-2 regulates the growth and differentiation of epithelial cells. It has previously been shown that the targets of SLURP-2 are various types of nicotinic acetylcholine receptors (nAChRs), as well as muscarinic acetylcholine receptors involved in the regulation of epithelial cell homeostasis. In this work, we found that the previously demonstrated acceleration of keratinocyte migration under the incubation with SLURP-2 is due to its interaction with α7 type nAChR. Using alanine scanning mutagenesis, we showed that the R20A mutation of the SLURP-2 molecule increases the inhibitory activity of SLURP-2 towards α7-nAChR and leads to an even greater stimulation of Het-1A keratinocyte migration, while, in contrast to SLURP-2, does not stimulate, but suppresses the proliferation of Het-1A cells. At the same time, other SLURP-2 mutations simultaneously lead to inhibition of α7-nAChR, proliferation and migration of keratinocytes. Thus, new information was obtained about the localization of regions of the SLURP-2 molecule, the replacement of which can lead to a targeted change in the biological activity of SLURP-2. Further research into the possibility of regulating the activity of SLURP-2 and the creation of targeted drugs based on it may be useful for the development of new drugs that stimulate wound healing.