Synthesis of Kisspeptin-Mimicking Fragments and Investigation of their Skin Anti-Aging Effects

Int J Mol Sci. 2020 Nov 10;21(22):8439. doi: 10.3390/ijms21228439.

Abstract

In recent years, a number of active materials have been developed to provide anti-aging benefits for skin and, among them, peptides have been considered the most promising candidate due to their remarkable and long-lasting anti-wrinkle activity. Recent studies have begun to elucidate the relationship between the secretion of emotion-related hormones and skin aging. Kisspeptin, a neuropeptide encoded by the KISS1 gene, has gained attention in reproductive endocrinology since it stimulates the reproductive axis in the hypothalamus; however, the effects of Kisspeptin on skin have not been studied yet. In this study, we synthesized Kisspeptin-10 and Kisspeptin-E, which are biologically active fragments, to mimic the action of Kisspeptin. Next, we demonstrated the anti-aging effects of the Kisspeptin-mimicking fragments using UV-induced skin aging models, such as UV-induced human dermal fibroblasts (Hs68) and human skin explants. Kisspeptin-E suppressed UV-induced 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) stimulation leading to a regulation of skin aging related genes, including type I procollagen, matrix metalloproteinases-1 (MMP-1), interleukin-6 (IL-6), and IL-8, and rescued the skin integrity. Taken together, these results suggest that Kisspeptin-E could be useful to improve UV-induced skin aging by modulating expression of stress related genes, such as 11β-HSD1.

Keywords: 11β-HSD1; Kisspeptin-mimicking fragments; MMP-1; collagen; skin aging.

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / genetics
  • Cell Line
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gene Expression / drug effects
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Kisspeptins / chemical synthesis*
  • Kisspeptins / chemistry
  • Kisspeptins / genetics
  • Kisspeptins / pharmacology*
  • Kisspeptins / physiology
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism
  • Models, Biological
  • Models, Molecular
  • Molecular Mimicry
  • Molecular Structure
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology
  • Protein Conformation
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Skin / drug effects
  • Skin / metabolism
  • Skin Aging / drug effects*
  • Skin Aging / genetics
  • Skin Aging / physiology
  • Skin Physiological Phenomena
  • Solid-Phase Synthesis Techniques
  • Tissue Culture Techniques
  • Ultraviolet Rays / adverse effects

Substances

  • CXCL8 protein, human
  • Collagen Type I
  • IL6 protein, human
  • Interleukin-6
  • Interleukin-8
  • KISS1 protein, human
  • Kisspeptins
  • Peptide Fragments
  • RNA, Messenger
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • HSD11B1 protein, human
  • MMP1 protein, human
  • Matrix Metalloproteinase 1