Increased angiogenesis by exosomes secreted by adipose-derived stem cells upon lipopolysaccharide stimulation

Shao Chun Wu, Pao Jen Kuo, Cheng Shyuan Rau, Lien Hung Huang, Chia Wei Lin, Yi Chan Wu, Chia Jung Wu, Chia Wen Tsai, Ting Min Hsieh, Hang Tsung Liu, Chun Ying Huang*, Ching Hua Hsieh*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

16 Scopus citations

Abstract

Exosomes secreted by adipose-derived stem cells (ADSCs) enhance angiogenesis and wound healing. However, in clinical settings, wounds may be infected by various bacteria or pathogens. We investigated whether human ADSCs stimulated with lipopolysaccharide (LPS) secrete exosomes (ADSC-LPS-exo) that augment the angiogenesis of human umbilical vein endothelial cells (HUVECs). ExoQuick-TC exosome precipitation solution was used to purify exosomes from human ADSC culture media in the presence or absence of 1 µg/mL LPS treatment for 24 h. The uptake of ADSC-LPS-exo significantly induced the activation of cAMP response element binding protein (CREB), activating protein 1 (AP-1), and nuclear factor-κB (NF-κB) signaling pathways and increased the migration of and tube formation in HUVECs. RNA interference with CREB, AP-1, or NF-κB1 significantly reduced the migration of and tube formation in HUVECs treated with ADSC-LPS-exo. An experiment with an antibody array for 25 angiogenesis-related proteins revealed that only interleukin-8 expression was significantly upregulated in HUVECs treated with ADSC-LPS-exo. In addition, proteomic analysis revealed that eukaryotic translation initiation factor 4E, amyloid beta A4 protein, integrin beta-1, and ras-related C3 botulinum toxin substrate 1 may be potential candidates involved in ADSC-LPS-exo-mediated enhanced angiogenesis.

Original languageEnglish
Article number8877
JournalInternational Journal of Molecular Sciences
Volume22
Issue number16
DOIs
StatePublished - 02 08 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Activating protein 1
  • Adipose-derived stem cells
  • Angiogenesis
  • CAMP response element binding protein
  • Endothelial cell
  • Exosome
  • Interleukin-8
  • Lipopolysaccharide
  • Nuclear factor-κB
  • Proteomic analysis

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