Lasers in Medical Science

, Volume 33, Issue 5, pp 1131–1145 | Cite as

Low-level laser irradiation at a high power intensity increased human endothelial cell exosome secretion via Wnt signaling

  • Hesam Saghaei Bagheri
  • Monireh Mousavi
  • Aysa Rezabakhsh
  • Jafar Rezaie
  • Seyed Hossein Rasta
  • Alireza Nourazarian
  • Çigir Biray Avci
  • Habib Tajalli
  • Mehdi Talebi
  • Ahmad Oryan
  • Majid Khaksar
  • Masoumeh Kazemi
  • Seyed Mahdi Nassiri
  • Shahrooz Ghaderi
  • Bakiye Goker Bagca
  • Reza Rahbarghazi
  • Emel Sokullu
Original Article


The distinct role of low-level laser irradiation (LLLI) on endothelial exosome biogenesis remains unclear. We hypothesize that laser irradiation of high dose in human endothelial cells (ECs) contributes to the modulation of exosome biogenesis via Wnt signaling pathway. When human ECs were treated with LLLI at a power density of 80 J/cm2, the survival rate reduced. The potential of irradiated cells to release exosomes was increased significantly by expressing genes CD63, Alix, Rab27a, and b. This occurrence coincided with an enhanced acetylcholine esterase activity, pseudopodia formation, and reduced zeta potential value 24 h post-irradiation. Western blotting showed the induction of LC3 and reduced level of P62, confirming autophagy response. Flow cytometry and electron microscopy analyses revealed the health status of the mitochondrial function indicated by normal ΔΨ activity without any changes in the transcription level of PINK1 and Optineurin. When cells exposed to high power laser irradiation, p-Akt/Akt ratio and in vitro tubulogenesis capacity were blunted. PCR array and bioinformatics analyses showed the induction of transcription factors promoting Wnt signaling pathways and GTPase activity. Thus, LLLI at high power intensity increased exosome biogenesis by the induction of autophagy and Wnt signaling. LLLI at high power intensity increases exosome biogenesis by engaging the transcription factors related to Wnt signaling and autophagy stimulate.


Human endothelial cells Low-level laser irradiation Exosome biogenesis Angiogenesis Wnt signaling pathway 



Authors are immensely grateful to the personnel of Stem Cell Research Center for guidance and help.

Funding source

This study was supported by a grant from Tabriz University of Medical Sciences, Tabriz, Iran.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All phase of in vitro assays in the current experiment was approved by the Ethics Committee of Tabriz University of Medical Sciences.

Supplementary material

10103_2018_2495_Fig7_ESM.gif (159 kb)
Fig. S1 Clustergram analysis (a), heat map graph of genes (b) involved in the Wnt signaling pathway. (GIF 159 kb)
10103_2018_2495_MOESM1_ESM.tif (4.5 mb)
High resolution image (TIFF 4558 kb)


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Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2018

Authors and Affiliations

  • Hesam Saghaei Bagheri
    • 1
  • Monireh Mousavi
    • 2
  • Aysa Rezabakhsh
    • 1
  • Jafar Rezaie
    • 1
  • Seyed Hossein Rasta
    • 3
    • 4
  • Alireza Nourazarian
    • 5
  • Çigir Biray Avci
    • 6
  • Habib Tajalli
    • 7
  • Mehdi Talebi
    • 8
  • Ahmad Oryan
    • 9
  • Majid Khaksar
    • 1
  • Masoumeh Kazemi
    • 1
  • Seyed Mahdi Nassiri
    • 10
  • Shahrooz Ghaderi
    • 11
  • Bakiye Goker Bagca
    • 6
  • Reza Rahbarghazi
    • 1
    • 12
  • Emel Sokullu
    • 13
    • 14
  1. 1.Stem Cell Research CenterTabriz University of Medical SciencesTabrizIran
  2. 2.Department of GeneticIslamic Azad UniversityAharIran
  3. 3.Medical Physics Department, Medical FacultyTabriz University of Medical SciencesTabrizIran
  4. 4.School of Medical SciencesUniversity of AberdeenAberdeenUK
  5. 5.Department of Biochemistry and Clinical Laboratories, Faculty of MedicineTabriz University of Medical SciencesTabrizIran
  6. 6.Department of Medical Biology, Faculty of MedicineEge UniversityIzmirTurkey
  7. 7.Research Institute for Applied Physics and AstronomyUniversity of TabrizTabrizIran
  8. 8.Hematology and Oncology Research CenterTabriz University of Medical SciencesTabrizIran
  9. 9.Department of Pathobiology, Faculty of Veterinary MedicineShiraz UniversityShirazIran
  10. 10.Department of Clinical Pathology, Faculty of Veterinary MedicineUniversity of TehranTehranIran
  11. 11.Department of Molecular Medicine, Faculty of Advanced Medical SciencesTabriz University of Medical SciencesTabrizIran
  12. 12.Department of Applied Cell Sciences, Faculty of Advanced Medical SciencesTabriz University of Medical SciencesTabrizIran
  13. 13.Bioengineering DepartmentIzmir Katip Celebi UniversityIzmirTurkey
  14. 14.Division of Biomedical Engineering at Brigham and Women’s Hospital, Harvard-MIT Health Sciences and TechnologyHarvard Medical SchoolCambridgeUSA

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