Exosomal miRNA derived from keratinocytes regulates pigmentation in melanocytes

J Dermatol Sci. 2019 Mar;93(3):159-167. doi: 10.1016/j.jdermsci.2019.02.001. Epub 2019 Mar 12.

Abstract

Background: Pigmentation is controlled by complex mechanisms. Evidence suggests that miRNAs can regulate pigmentation. However, the mechanism has not been fully elucidated. Objective In this study, we revealed a novel mechanism that regulates pigmentation involving exosomes, miRNAs and the crosstalk between keratinocytes and melanocytes.

Methods: The expression and localization of exosome specific marker TSG101 in keratinocytes and melanocytes; Changes of melanin content in melanocytes after co-culture of exosome and melanocytes; Expression changes of target gene TYR and its related genes and inhibitory effect of miR-330-5p on pigmentation were studied by using various molecular biological techniques.

Results: In this experiment, we used miR-330-5p in keratinocytes to verify the effect of keratinocyte derived exosome on melanocyte pigmentation. First, we found that keratinocytes secrete exosomes carrying miR-330-5p; moreover, greater miR-330-5p expression was found in exosomes derived from keratinocytes that overexpressed miR-330-5p. Second, we found that exosomes derived from keratinocytes with overexpression of miR-330-5p caused a significant increase in miR-330-5p in melanocytes. Finally, exosomes derived from keratinocytes that overexpressed miR-330-5p induced a significant decrease in the production of melanin and expression of TYR in melanocytes. Meanwhile, we overexpressed miR-330-5p in melanocytes, which also proved the inhibitory effect of miR-330-5p on pigmentation.

Conclusion: These findings suggest that keratinocytes crosstalk with melanocytes in the epidermal melanin unit via exosomal miRNAs. These studies reveal an important role of exosomes in melanocyte pigmentation, which opens a new pathway of melanogenesis.

Keywords: Exosome; Keratinocyte; Melanocyte.

MeSH terms

  • Animals
  • Cell Communication / genetics*
  • Cell Culture Techniques
  • Cell Line
  • Coculture Techniques
  • DNA-Binding Proteins / metabolism
  • Endosomal Sorting Complexes Required for Transport / metabolism
  • Exosomes / metabolism
  • Keratinocytes / cytology
  • Keratinocytes / metabolism*
  • Melanins / metabolism
  • Melanocytes / metabolism*
  • Mice
  • MicroRNAs / metabolism*
  • Monophenol Monooxygenase / genetics
  • Monophenol Monooxygenase / metabolism
  • Skin Pigmentation / genetics*
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • Endosomal Sorting Complexes Required for Transport
  • MIRN330 microRNA, mouse
  • Melanins
  • MicroRNAs
  • Transcription Factors
  • Tsg101 protein
  • Monophenol Monooxygenase