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

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Abstract

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.

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  • 28 November 2019

    After publication of this paper, the authors determined an error in Fig.��4. Below is the correct Fig.��4.

References

  1. Rezaie J, Mehranjani MS, Rahbarghazi R, Shariatzadeh MA Angiogenic and restorative abilities of human Mesenchymal stem cells were reduced following treatment with serum from diabetes mellitus type 2 patients. J Cell Biochem n/a-n/a. https://doi.org/10.1002/jcb.26211

  2. Hassanpour M, Rezabakhsh A, Rahbarghazi R, Nourazarian A, Nouri M, Avci ÇB, Ghaderi S, Alidadyani N, Bagca BG, Bagheri HS (2017) Functional convergence of Akt protein with VEGFR-1 in human endothelial progenitor cells exposed to sera from patient with type 2 diabetes mellitus. Microvasc Res 114:101–113

    Article  PubMed  CAS  Google Scholar 

  3. Roskoski R (2017) Vascular endothelial growth factor (VEGF) and VEGF receptor inhibitors in the treatment of renal cell carcinomas. Pharmacol Res

  4. Hoff PM, Machado KK (2012) Role of angiogenesis in the pathogenesis of cancer. Cancer Treat Rev 38(7):825–833

    Article  PubMed  CAS  Google Scholar 

  5. Ziyad S, Iruela-Arispe ML (2011) Molecular mechanisms of tumor angiogenesis. Genes Cancer 2(12):1085–1096. https://doi.org/10.1177/1947601911432334

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Chen Q-H, Liu A-R, Qiu H-B, Yang Y (2015) Interaction between mesenchymal stem cells and endothelial cells restores endothelial permeability via paracrine hepatocyte growth factor in vitro. Stem Cell Res Ther 6(1):44

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. van Balkom BW, De Jong OG, Smits M, Brummelman J, den Ouden K, de Bree PM, van Eijndhoven MA, Pegtel DM, Stoorvogel W, Würdinger T (2013) Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells. Blood 121(19):3997–4006

    Article  PubMed  CAS  Google Scholar 

  8. Mulcahy LA, Pink RC, Carter DRF (2014) Routes and mechanisms of extracellular vesicle uptake. J Extracell Vesicles 3. https://doi.org/10.3402/jev.v3.24641

  9. Ribeiro MF, Zhu H, Millard RW, Fan G-C (2013) Exosomes function in pro-and anti-angiogenesis. Curr Angiogenesis 2(1):54

    CAS  Google Scholar 

  10. Rezaie J, Ajezi S, Avci ÇB, Karimipour M, Geranmayeh MH, Nourazarian A, Sokullu E, Rezabakhsh A, Rahbarghazi R (2017) Exosomes and their application in biomedical field: difficulties and advantages. Mol Neurobiol. https://doi.org/10.1007/s12035-017-0582-7

  11. Sarko DK, McKinney CE (2017) Exosomes: origins and therapeutic potential for neurodegenerative disease. Front Neurosci 11

  12. Keller S, Ridinger J, Rupp A-K, Janssen JWG, Altevogt P (2011) Body fluid derived exosomes as a novel template for clinical diagnostics. J Transl Med 9:86–86. https://doi.org/10.1186/1479-5876-9-86

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Alenquer M, Amorim MJ (2015) Exosome biogenesis, regulation, and function in viral infection. Viruses 7(9):5066–5083. https://doi.org/10.3390/v7092862

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Ottaviani G, Martinelli V, Rupel K, Caronni N, Naseem A, Zandonà L, Perinetti G, Gobbo M, Di Lenarda R, Bussani R (2016) Laser therapy inhibits tumor growth in mice by promoting immune surveillance and vessel normalization. EBioMedicine 11:165–172

    Article  PubMed  PubMed Central  Google Scholar 

  15. Akbarzadeh M, Nouri M, Banekohal MV, Cheraghi O, Tajalli H, Movassaghpour A, Soltani S, Cheraghi H, Feizy N, Montazersaheb S (2016) Effects of combination of melatonin and laser irradiation on ovarian cancer cells and endothelial lineage viability. Lasers Med Sci 31(8):1565–1572

    Article  PubMed  Google Scholar 

  16. Dias FJ, Issa JPM, Barbosa APA, de Vasconcelos PB, Watanabe I-S, MizusakiIyomasa M (2012) Effects of low-level laser irradiation in ultrastructural morphology, and immunoexpression of VEGF and VEGFR-2 of rat masseter muscle. Micron 43(2):237–244

    Article  PubMed  CAS  Google Scholar 

  17. Karu TI (2008) Mitochondrial signaling in mammalian cells activated by red and near-IR radiation. Photochem Photobiol 84(5):1091–1099

    Article  PubMed  CAS  Google Scholar 

  18. Huang L, Wu S, Xing D (2011) High fluence low-power laser irradiation induces apoptosis via inactivation of Akt/GSK3β signaling pathway. J Cell Physiol 226(3):588–601

    Article  PubMed  CAS  Google Scholar 

  19. Rezabakhsh A, Cheraghi O, Nourazarian A, Hassanpour M, Kazemi M, Ghaderi S, Faraji E, Rahbarghazi R, Avci ÇB, Bagca BG, Garjani A (2017) Type 2 diabetes inhibited human Mesenchymal stem cells Angiogenic response by over-activity of the Autophagic pathway. J Cell Biochem 118(6):1518–1530. https://doi.org/10.1002/jcb.25814

    Article  PubMed  CAS  Google Scholar 

  20. Kook S, Zhan X, Cleghorn W, Benovic J, Gurevich V, Gurevich E (2014) Caspase-cleaved arrestin-2 and BID cooperatively facilitate cytochrome C release and cell death. Cell Death Differ 21(1):172

    Article  PubMed  CAS  Google Scholar 

  21. Yi M, Parthiban P, Hwang J, Zhang X, Jeong H, Park DH, Kim D-K (2014) Effect of a bispidinone analog on mitochondria-mediated apoptosis in HeLa cells. Int J Oncol 44(1):327–335

    Article  PubMed  CAS  Google Scholar 

  22. Góralczyk K, Szymańska J, Łukowicz M, Drela E, Kotzbach R, Dubiel M, Michalska M, Góralczyk B, Zając A, Rość D (2015) Effect of LLLT on endothelial cells culture. Lasers Med Sci 30(1):273–278. https://doi.org/10.1007/s10103-014-1650-0

    Article  PubMed  Google Scholar 

  23. Bobrie A, Colombo M, Krumeich S, Raposo G, Théry C (2012) Diverse subpopulations of vesicles secreted by different intracellular mechanisms are present in exosome preparations obtained by differential ultracentrifugation. J Extracell Vesicles 1. https://doi.org/10.3402/jev.v1i0.18397

  24. Jelonek K, Widlak P, Pietrowska M (2016) The influence of ionizing radiation on Exosome composition, secretion and intercellular communication. Protein Pept Lett 23(7):656–663. https://doi.org/10.2174/0929866523666160427105138

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Al Musawi MS, Jaafar MS, Al-Gailani B, Ahmed NM, Suhaimi FM (2017) Laser-induced changes of in vitro erythrocyte sedimentation rate. Lasers Med Sci. https://doi.org/10.1007/s10103-017-2340-5

  26. Fernandes HP, Cesar CL, Barjas-Castro ML (2011) Electrical properties of the red blood cell membrane and immunohematological investigation. Rev Bras Hematol Hemoter 33(4):297–301. https://doi.org/10.5581/1516-8484.20110080

    Article  PubMed  PubMed Central  Google Scholar 

  27. Chang Z, Shi G, Jin J, Guo H, Guo X, Luo F, Song Y, Jia X (2013) Dual PI3K/mTOR inhibitor NVP-BEZ235-induced apoptosis of hepatocellular carcinoma cell lines is enhanced by inhibitors of autophagy. Int J Mol Med 31(6):1449–1456

    Article  PubMed  CAS  Google Scholar 

  28. Chen Y-D, Fang Y-T, Cheng Y-L, Lin C-F, Hsu L-J, Wang S-Y, Anderson R, Chang C-P, Lin Y-S (2017) Exophagy of annexin A2 via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cells. Sci Rep 7

  29. Rohringer S, Holnthoner W, Chaudary S, Slezak P, Priglinger E, Strassl M, Pill K, Mühleder S, Redl H, Dungel P (2017) The impact of wavelengths of LED light-therapy on endothelial cells. Sci Rep 7

  30. Ricci R, Pazos M, Borges RE, Pacheco-Soares C (2009) Biomodulation with low-level laser radiation induces changes in endothelial cell actin filaments and cytoskeletal organization. J Photochem Photobiol B Biol 95(1):6–8

    Article  CAS  Google Scholar 

  31. Góralczyk K, Szymańska J, Linkowska K, Ruszkowska-Ciastek B, Gryko Ł, Zając A, Grzybowski T, Rość D (2014) Effect of low level laser irradiation on VEGF gene expression in cultured endothelial cells. Med Res J 2(2):61–65

    Google Scholar 

  32. Gross JC, Chaudhary V, Bartscherer K, Boutros M (2012) Active Wnt proteins are secreted on exosomes. Nat Cell Biol 14(10):1036–1045

    Article  PubMed  CAS  Google Scholar 

  33. Koles K, Budnik V (2012) Exosomes go with the Wnt. Cell Logist 2(3):169–173

    Article  PubMed  PubMed Central  Google Scholar 

  34. Cerpa W, Godoy JA, Alfaro I, Farías GG, Metcalfe MJ, Fuentealba R, Bonansco C, Inestrosa NC (2008) Wnt-7a modulates the synaptic vesicle cycle and synaptic transmission in hippocampal neurons. J Biol Chem 283(9):5918–5927. https://doi.org/10.1074/jbc.M705943200

    Article  PubMed  CAS  Google Scholar 

  35. Derkus B, Emregul KC, Emregul E (2017) A new approach in stem cell research-Exosomes: their mechanism of action via cellular pathways. Cell Biol Int

  36. Hyenne V, Labouesse M, Goetz JG (2016) The small GTPase Ral orchestrates MVB biogenesis and exosome secretion. Small GTPases:1–7

  37. Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, Moita CF, Schauer K, Hume AN, Freitas RP (2010) Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 12(1):19

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

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.

Author information

Author notes

  1. Reza Rahbarghazi and Emel Sokullu contributed equally to this work.

Authors and Affiliations

  1. Stem Cell Research Center, Tabriz University of Medical Sciences, Imam Reza St., Golgasht St, Tabriz, 5166614756, Iran

    Hesam Saghaei Bagheri, Aysa Rezabakhsh, Jafar Rezaie, Majid Khaksar, Masoumeh Kazemi & Reza Rahbarghazi

  2. Department of Genetic, Islamic Azad University, Ahar Branch, Ahar, Iran

    Monireh Mousavi

  3. Medical Physics Department, Medical Faculty, Tabriz University of Medical Sciences, Tabriz, Iran

    Seyed Hossein Rasta

  4. School of Medical Sciences, University of Aberdeen, Aberdeen, UK

    Seyed Hossein Rasta

  5. Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Alireza Nourazarian

  6. Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey

    Çigir Biray Avci & Bakiye Goker Bagca

  7. Research Institute for Applied Physics and Astronomy, University of Tabriz, Tabriz, Iran

    Habib Tajalli

  8. Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Mehdi Talebi

  9. Department of Pathobiology, Faculty of Veterinary Medicine, Shiraz University, Shiraz, Iran

    Ahmad Oryan

  10. Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

    Seyed Mahdi Nassiri

  11. Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Shahrooz Ghaderi

  12. Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Reza Rahbarghazi

  13. Bioengineering Department, Izmir Katip Celebi University, 35100, Izmir, Turkey

    Emel Sokullu

  14. Division of Biomedical Engineering at Brigham and Women’s Hospital, Harvard-MIT Health Sciences and Technology, Harvard Medical School, Cambridge, MA, USA

    Emel Sokullu

Authors
  1. Hesam Saghaei Bagheri
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Corresponding authors

Correspondence to Reza Rahbarghazi or Emel Sokullu.

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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.

Additional information

Hesam Saghaei Bagheri, Monireh Mousavi, and Alireza Nourazarian are considered equally as co-first authors.

Electronic supplementary material

Fig. S1

Clustergram analysis (a), heat map graph of genes (b) involved in the Wnt signaling pathway. (GIF 159 kb)

High resolution image (TIFF 4558 kb)

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Bagheri, H.S., Mousavi, M., Rezabakhsh, A. et al. Low-level laser irradiation at a high power intensity increased human endothelial cell exosome secretion via Wnt signaling. Lasers Med Sci 33, 1131–1145 (2018). https://doi.org/10.1007/s10103-018-2495-8

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