Saliva exosomes-derived UBE2O mRNA promotes angiogenesis in cutaneous wounds by targeting SMAD6

J Nanobiotechnology. 2020 May 6;18(1):68. doi: 10.1186/s12951-020-00624-3.

Abstract

Background: Enhancing angiogenesis is critical for accelerating wound healing. Application of different types of exosomes (Exos) to promote angiogenesis represents a novel strategy for enhanced wound repair. Saliva is known to accelerate wound healing, but the underlying mechanisms remain unclear.

Results: Our results have demonstrated that saliva-derived exosomes (saliva-Exos) induce human umbilical vein endothelial cells (HUVEC) proliferation, migration, and angiogenesis in vitro, and promote cutaneous wound healing in vivo. Further experiments documented that Ubiquitin-conjugating enzyme E2O (UBE2O) is one of the main mRNAs of saliva-Exos, and activation of UBE2O has effects similar to those of saliva-Exos, both in vitro and in vivo. Mechanistically, UBE2O decreases the level of SMAD family member 6 (SMAD6), thereby activating bone morphogenetic protein 2 (BMP2), which, in turn, induces angiogenesis.

Conclusions: The present work suggests that administration of saliva-Exos and UBE2O represents a promising strategy for enhancing wound healing through promotion of angiogenesis.

Keywords: Angiogenesis; Exosome; SMAD6; Saliva; UBE2O; Wound.

MeSH terms

  • Animals
  • Cells, Cultured
  • Exosomes / enzymology*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Mice
  • Neovascularization, Physiologic / drug effects*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Messenger / pharmacology
  • Saliva / cytology
  • Saliva / enzymology*
  • Skin / injuries
  • Smad6 Protein / metabolism*
  • Ubiquitin-Conjugating Enzymes* / genetics
  • Ubiquitin-Conjugating Enzymes* / metabolism
  • Ubiquitin-Conjugating Enzymes* / pharmacology
  • Wound Healing / drug effects

Substances

  • RNA, Messenger
  • SMAD6 protein, human
  • Smad6 Protein
  • Ubiquitin-Conjugating Enzymes
  • UBE2O protein, human