Shlepova O V, Gornostaeva T Ya, Kukushkin I D, Azev V N, Bychkov M L, Shenkarev Z O, Kirpichnikov M P, Lyukmanova E N
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997 Russian Federation.
Moscow Center for Advanced Studies, Moscow, 123592 Russian Federation.
Acta Naturae. 2024 Oct-Dec;16(4):86-94. doi: 10.32607/actanaturae.27494.
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.
分泌型人类蛋白SLURP-2是上皮细胞稳态的调节因子，可增强角质形成细胞的活力和迁移能力。SLURP-2在角质形成细胞中的作用靶点是烟碱型和毒蕈碱型乙酰胆碱受体。这项工作致力于寻找负责增强角质形成细胞活力和迁移能力的SLURP-2功能区域。我们制备了与SLURP-2环区相对应的合成肽，并分别使用WST-8试验和划痕试验研究了它们对HaCaT皮肤角质形成细胞活力和迁移的影响。一种模拟环II的肽表现出最高活性，它增强了角质形成细胞的活力并刺激了它们的迁移。该肽的活性是通过与α7-和α3β2-nAChRs相互作用以及抑制p38 MAPK细胞内信号通路介导的。因此，我们获得了新的数据，解释了SLURP-2调节活性的潜在机制，并表明进一步研究模拟环II的肽作为伤口愈合药物原型的前景。
