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Lasers in Medical Science

, Volume 34, Issue 7, pp 1465–1472 | Cite as

Photobiomodulation therapy modulates epigenetic events and NF-κB expression in oral epithelial wound healing

  • Amanda de Farias Gabriel
  • Vivian Petersen Wagner
  • Cintia Correa
  • Liana Preto Webber
  • Emily Ferreira Salles Pilar
  • Marina Curra
  • Vinicius Coelho Carrard
  • Marco Antonio Trevizani Martins
  • Manoela Domingues MartinsEmail author
Original Article

Abstract

The aim of this study was to evaluate the effect of photobiomodulation therapy (PBMT) on histone 3 acetylation (acH3) and NF-κB expression during oral ulcer healing. A total of 48 male Wistar rats were divided into control group (CG) and PBMT group (n = 24 each). Traumatic ulcers were created in the dorsum of the rats’ tongue with a punch tool. Irradiation with InGaAlP laser, 660 nm, 40 mW, 0.04 cm2 spot size, 4 J/cm2, 4 s, and 0.16 J per spot was performed once a day in close contact for 10 consecutive days. CG received only daily handling. Rats were euthanized on days 3, 5, and 10 (n = 8) and were monitored daily to assess wound status. Immunohistochemical analysis for acH3 and NF-κB detection was performed. One thousand epithelial cells were counted, and mean acH3- and NF-κB-positive cells were calculated and compared between the groups. PBMT accelerated the repair of oral ulcers. On day 3, PBMT showed significantly higher means for acH3- and NF-κB-positive cells than CG. On day 5, no difference was observed between the groups concerning both markers. On day 10, PBMT presented lower acH3 and NF-κB means than the control group. We concluded that PBMT stimulates keratinocyte migration in the early stage of oral wound healing and keratinocyte differentiation at the final stage by modulating histone acetylation and NF-κB expression.

Keywords

Low-level laser therapy Diode laser Repair Histone acetylase enzyme Histones deacetylase enzyme 

Notes

Acknowledgments

The authors are grateful to Marta Justina Giotti Cioato and Flavia Rejane Giusti for technical support.

Funding information

This study was funded by the Postgraduate Research Group of Porto Alegre Clinics Hospital (GPPG/FIPE: 2014-0534), Brazilian National Council for Scientific and Technological Development (CNPq student scholarship), Children’s Cancer Institute (student scholarship), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil(CAPES)-finance code 001. Manoela Domingues Martins is a research fellow funded by the Brazilian National Council for Scientific and Technological Development (CNPq).

Compliance with ethical standards

The study was approved by the ethics committee of Porto Alegre Clinics Hospital (Brazil) under process number 14-0534. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed involving animals were in accordance with the ethical standards of the institution, which the study was conducted.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Scully C, Felix DH (2005) Oral medicine-update for the dental practitioner. Aphthous and other common ulcers. Br Dent J 199(5):259–264Google Scholar
  2. 2.
    de Mendonça RJ, Coutinho-Netto J (2009) Cellular aspects of wound healing. An Bras Dermatol 84(3):257–262Google Scholar
  3. 3.
    Wagner VP, Meuer L, Martins MAT, Danilevicz CK, Magnusson AS, Marques MM, Filho MS, Squarize CH, Martins MD (2013) Influence of different energy densities of laser phototherapy on oral wound healing. J Biomed Opt 18(2):128002Google Scholar
  4. 4.
    Dongong TI, Meirong LU, Xiaobing FU, Weindon H (2014) Causes and consequences of epigenetic regulation in wound healing. Wound Rep Reg 22(3):305–312Google Scholar
  5. 5.
    Gonzalez AC, Costa TF, Andrade ZA, Medrado AR (2016) Wound healing - a literature review. An Bras Dermatol 91(5):614–620Google Scholar
  6. 6.
    Maver T, Maver U, Stana Kleinschek K, Smrke DM, Kreft S (2015) A review of herbal medicines in wound healing. Int J Dermatol 54(7):740–751Google Scholar
  7. 7.
    Spallota F, Cencioni C, Straino S, Sbardella G, Castellano S, Capogrossi MC, Martelli F, Gaetano C (2013) Enhancement of lysine acetylation accelerates wound repair. Communicative & Integrative Biology 6(5):e25466Google Scholar
  8. 8.
    Martins MD, Castilhos R (2013) Histones: Controlling Tumor Signaling Circuitry. J Carcinog Mutagen 1(5):1–12Google Scholar
  9. 9.
    Wade PA, Kikyo N (2002) Chromatin remodeling in nuclear cloning. Eur J Biochem 269(9):2284–2287Google Scholar
  10. 10.
    Zhou R, Gong A-Y, Chen D, Myler RE, Eischeid AN, Chen XM (2013) Histone deacetylases and NF-kB signaling coordinate expression of CX3CL1 in epithelial cells in response to microbial challenge by suppressing miR-424 and miR-503. Plos One 8(5):e65153Google Scholar
  11. 11.
    Lawrence T (2009) The nuclear factor NFk-B pathway in inflammation. Cold Spring Harb Perspect Biol 1(6):1–10Google Scholar
  12. 12.
    Aupperle KR, Bennett BL, Boyle DL, Tak PP, Manning AM, Firestein GS (1999) NF-kappa B regulation by I kappa B kinase in primary fibroblast-like synoviocytes. J Immunol 163(1):427–433Google Scholar
  13. 13.
    Scully C, Shotts R (2000) Mouth ulcers and other causes of orofacial soreness and pain. BMJ 321(7254):162–165Google Scholar
  14. 14.
    Field EA, Allan RB (2003) Review article: oral ulceration – etiopathogenesis, clinical diagnosis and management in the gastrointestinal clinic. Aliment Pharmacol Ther 18(10):949–962Google Scholar
  15. 15.
    Martins MD, Fernandes KPS, Pavesi VC, França MC, Mesquita-Ferrari RA, Bussadori SK (2011) Healing properties of papain-based gel on oral ulcers. Braz J Oral Sci 10(1):120–123Google Scholar
  16. 16.
    Bourguignon-filho AM Feitosa ACR, Beltrão GC, Pagnoncelli RM (2005) Utilização do laser de baixa intensidade no processo de cicatrização tecidual. Revisão de literatura. Revista Portuguesa de Estomatologia, Medicina Dentária e Cirurgia Maxilofacial 46(1): 37-43Google Scholar
  17. 17.
    Eduardo FP, Mehnert TU, Monezi TA, Zezzel DM (2007) Cultured epithelial cells response to phototherapy. Lasers Surg Med 39(4):365–272Google Scholar
  18. 18.
    Baptista J, Martins MD, Pavesi VCS, Bussadori SK, Fernandes KPS, Pinto Júnior DS, Ferrari RAM (2011) Influence of laser photobiomodulation on collagen IV during skeletal muscle tissue remodeling after injury in rats. Photomedicine and Laser Surgery 29(1):11–17Google Scholar
  19. 19.
    Wagner VP, Curra M, Webber LP, Nor C, Matte U, Meuer L, Martins MD (2016) Photobiomodulation regulates cytokine release and new blood vessel formation during oral wound healing in rats. Lasers Med Sci 31(4):665–671Google Scholar
  20. 20.
    Pellicioli AC, Martins MD, Dillenburg CS, Marques MM, Squarize CH, Castilho RM (2014) Laser phototherapy accelerates oral keratinocyte migration through the modulation of the mammalian target of rapamycin signaling pathway. J Biomed Opt 19(2):028002Google Scholar
  21. 21.
    Castilho RM, Squarize CH, Gutkind JS (2013) Exploiting Pl3K/Mtor signaling to accelerate epithelial wound healing. Oral Dis 19(6):551–558Google Scholar
  22. 22.
    Corazza AV, Jorge J, Kurachi C, Bagnato VS (2007) Photobiomodulation on the angiogenesis of skin wounds in rats using different light sources. Photomed Laser Surg 25(2):102–106Google Scholar
  23. 23.
    Tang E, Khan I, Andreana S, Arany PR (2017) Laser-activated transforming growth factor-β1 induces human β-defensin 2: implications for laser therapies for periodontitis and peri-implantitis. J Periodontal Res 52(3):360–367Google Scholar
  24. 24.
    Sperandio FF, Simões A, Corrêa L, Aranha AC, Giudice FS, Hamblin MR, Sousa SC (2015) Low-level laser irradiation promotes the proliferation and maturation of keratinocytes during epithelial wound repair. J Biophotonics 8(10):795–803Google Scholar
  25. 25.
    Antunes HS, Wajnberg G, Pinho MB, Jorge NAN, de Moraes JLM, Stefanoff CG, Herchenhorn D, Araújo CMM, Viégas CMP, Rampini MP, Dias FL, de Araujo-Souza PS, Passetti F, Ferreira CG (2018) cDNA microarray analysis of human keratinocytes cells of patients submitted to chemoradiotherapy and oral photobiomodulation therapy: pilot study. Lasers Med Sci 33(1):11–18Google Scholar
  26. 26.
    Marín-Conde F, Castellanos-Cosano L, Pachón-Ibañez J, Serrera-Figallo MA, Gutiérrez-Pérez JL, Torres-Lagares D (2018) Photobiomodulation with low-level laser therapy reduces oral mucositis caused by head and neck radio-chemotherapy: prospective randomized controlled trial. Int J Oral Maxillofac Surg S0901-5027(18):30475–30472Google Scholar
  27. 27.
    Engel KW, Khan I, Arany PR (2016) Cell lineage responses to photobiomodulation therapy. J Biophotonics 9(11-12):1148–1156 zGoogle Scholar
  28. 28.
    Huynha NC-N, Evertsb V, Ampornaramveth RS (2017) Histone deacetylases and their roles in mineralized tissue regeneration. Bone Rep 16(7):33–40Google Scholar
  29. 29.
    Zeybel M, Hardy T, Wong YK, Mathers JC, Fox CR, Gackowska A, Oakley F, Burt AD, Wilson CL, Anstee QM, Barter MJ, Masson S, Elsharkawy AM, Mann DA, Mann J (2012) Multigenerational epigenetic adaptation of the hepatic wound-healing response. Nat Med 18(9):1369–1377Google Scholar
  30. 30.
    Mann J, Mann DA (2013) Epigenetic regulation of wound healing and fibrosis. Curr Opin Rheumatol 25(1):101–107Google Scholar
  31. 31.
    Lewis CJ, Mardaryev AN, Sharov AA, Fessing MY, Botchkarev VA (2014) The epigenetic regulation of wound healing. Adv Wound Care 3(7):468–474Google Scholar
  32. 32.
    Feinberg AP (2010) Genome-scale approaches to the epigenetics of common human disease. Virchows Arch 456(1):13–21Google Scholar
  33. 33.
    Robertson ED, Weir L, Romanowska M, Leigh IM, Panteleyev AA (2012) ARNT controls the expression of epidermal differentiation genes through HDAC- and EGFR-dependent pathways. J Cell Sci 125(Pt 14):3320–3332Google Scholar
  34. 34.
    LeBoeuf M, Terrell A, Trivedi S, Sinha S, Epstein JA, Olson EN, Morrisey EE, Millar SE (2010) Hdac1 and Hdac2 act redundantly to control p63 and p53 functions in epidermal progenitor cells. Dev Cell 19(6):807–818Google Scholar
  35. 35.
    Chen AC-H, Arany PR, Huang Y-Y, Tomkinson EM, Sharma SK, Kharkwal GB, Saleem T, Mooney D, Yull FE, Blackwell TS, Hamblin MR (2011) Low-level laser therapy activates NF-kB via generation of reactive oxygen species in mouse embryonic fibroblasts. PLoS ONE 6(7):e22453Google Scholar
  36. 36.
    Egan LJ, de LA, Lehrman ED, Myhre GM, Eckmann L, Kagnoff MF (2003) Nuclear fator NF-kB activation promotes restitution of wounded intestinal epithelial monolayers. Am J Physiol Cell Physiol 285(5):C1028–C1035Google Scholar
  37. 37.
    Badr CE, Niers JM, Tjon-Kon-Fat LA, Noske DP, Wurdinger T, Tannous BA (2009) Real-time monitoring of nuclear factor kappaB activity in cultured cells and in animal models. Mol. Imaging 8(5):278–290Google Scholar
  38. 38.
    Rahmana I, Marwickb J, Kirkhamc P (2004) Redox modulation of chromatin remodeling: impact on histone acetylation and deacetylation, NF-kB and pro-inflammatory gene expression. Biochem Pharmacol 68(6):1255–1267Google Scholar
  39. 39.
    Na J, Lee K, Na W, Shin J-Y, Lee M-J, Yune TY, Lee HK, Jung H-S, Kim WS, Ju B-G (2016) Histone H3K27 Demethylase JMJD3 in cooperation with NF-kB regulates keratinocyte wound healing. J Investig Dermatol 136(4):847–858Google Scholar
  40. 40.
    Na J, Shin JY, Jeong H, Lee JY, Kim BJ, Kim WS, Yune TY, Ju B-G (2017) JMJD3 and NF-κB-dependent activation of Notch1 gene is required for keratinocyte migration during skin wound healing. Sci Rep N7(1):6494Google Scholar
  41. 41.
    Curra M, Pellicioli ACA, Kretzmann Filho NA, Ochs G, Matte U, Sant’Ana Filho M, Martins MAT, Martins MD (2015) Photobiomodulation reduces oral mucositis by modulating NF-kB. J Biomed Opt 20(12):125008Google Scholar
  42. 42.
    Adams S, Pankow S, Werner S, Munz B (2007) Regulation of NF-kB activity and keratinocyte differentiation by the RIP4 protein: Implications for cutaneous wound repair. J Investig Dermatol 127(3):538–544Google Scholar

Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2019

Authors and Affiliations

  • Amanda de Farias Gabriel
    • 1
  • Vivian Petersen Wagner
    • 1
    • 2
  • Cintia Correa
    • 1
  • Liana Preto Webber
    • 1
    • 3
  • Emily Ferreira Salles Pilar
    • 4
  • Marina Curra
    • 5
  • Vinicius Coelho Carrard
    • 1
    • 6
  • Marco Antonio Trevizani Martins
    • 6
  • Manoela Domingues Martins
    • 1
    • 2
    • 4
    • 6
    Email author
  1. 1.Department of Oral Pathology, School of DentistryFederal University of Rio Grande do SulPorto AlegreBrazil
  2. 2.Department of Oral Diagnosis, Piracicaba Dental SchoolUniversity of CampinasPiracicabaBrazil
  3. 3.Laboratory of Epithelial Biology, Department of Periodontics and Oral MedicineUniversity of Michigan School of DentistryAnn ArborUSA
  4. 4.Experimental Pathology Unit, Clinics Hospital of Porto AlegreFederal University of Rio Grande do SulPorto AlegreBrazil
  5. 5.School of DentistryUniversity of Caxias do SulCaxias do SulBrazil
  6. 6.Department of Oral MedicinePorto Alegre Clinics Hospital (HCPA/UFRGS)Porto AlegreBrazil

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