Participation of the Immune System and Hedgehog Signaling in Neoangiogenesis Under Laser Photobiomodulation
Journal of Lasers in Medical Sciences,
Vol. 10 No. 4 (2019),
1 October 2019
,
Page 310-316
Abstract
Introduction:
This study aimed to characterize immune and endothelial cells, myofibroblasts and pericytes, and positive cells for hedgehog proteins in late tissue repair of rats skin wounds treated with 670 nm photobiomodulation therapy (PBMT).
Methods:
A blind experimental study was conducted, in order to assess the effect of PBMT in later stages of healing, with emphasis on neoangiogenesis, immune cells and Hedgehog signaling. Forty Wistar rats were allocated randomly in two groups; control and treated with a diode GaAlAs laser (9 mW, 670 nm, 0.031 W/cm², spot size of 0.28 cm², fluence of 4 J/ cm2 applied every other day, until a total dose of 16 J/cm2 was achieved). Standardized skin wounds were performed and the animals were euthanized at 14, 21, 28 and 35 days. Tissue sections were subjected to hematoxylin-eosin and immunohistochemistry for CD31, NG2, smooth muscle alpha actin, CD8, CD68, Ptch, Gli-2 and Ihh. All histomorphometric data were statistically analyzed and significance level was at P < 0.05.
Results:
At late stages of wound healing, neoangiogenesis persisted as revealed for the number of CD31+ cells (P = 0.016) and NG2+ and smooth muscle alpha actin positive pericytes (P = 0.025), for both experimental groups. By day 21, laser-treated group had decreased CD68+ cells (P = 0.032) and increased CD8+ (P=0.038). At remodeling stage, there were positive cells for the hedgehog signaling pathway family which seemed to be activated.
Conclusion:
These data suggest that photobiomodulation therapy was able to modulate extracellular matrix remodelling even at the later stages of wound healing.
- Wound healing
- Low-level light therapy
- Immunohistochemistry
- Neoangiogenesis.
How to Cite
References
Medrado AP, Soares AP, Santos ET, Reis SR, Andrade ZA. Influence of laser photobiomodulation upon connective tissue remodeling during wound healing. J Photochem Photobiol B: Biol. 2008 Sep 18;92(3):144-52.
Reis SR, Medrado AP, Marchionni AM, Figueira C, Fracassi LD, Knop LA. Effect of 670-nm laser therapy and dexamethasone on tissue repair: a histological and ultrastructural study. Photomed Laser Surg. 2008 Aug 1;26(4):307-13.
Loreti EH, Pascoal VL, Nogueira BV, Silva IV, Pedrosa DF. Use of laser therapy in the healing process: a literature review. Photomed Laser Surg. 2015 Feb 1;33(2):104-16. doi:10.1089/pho.2014.3772
Fortuna T, Gonzalez AC, Ferreira MS, Reis SR, Medrado AA. Biomodulatory potential of low-level laser on neoangiogenesis and remodeling tissue. A literature review. J Public Health Dent. 2018 Jun 25;9(1):95-103. doi: 10.17267/2596-3368
Fortuna T, Gonzalez AC, Sá MF, Andrade ZD, Reis SR, Medrado AR. Effect of 670 nm laser photobiomodulation on vascular density and fibroplasia in late stages of tissue repair. Int Wound J. 2018 Apr;15(2):274-82. doi: 10.1111/iwj.12861
Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res. 2009 Oct;37(5):1528-42. doi: 10.1177/147323000903700531
Delavary BM, van der Veer WM, van Egmond M, Niessen FB, Beelen RH. Macrophages in skin injury and repair. Immunobiology. 2011 Jul 1;216(7):753-62. doi: 10.1016/j.imbio.2011.01.001
Ingham PW, Nakano Y, Seger C. Mechanisms and functions of Hedgehog signaling across the metazoa. Nature reviews genetics. 2011 Jun;12(6):393.
Byrd N, Grabel L. Hedgehog signaling in murine vasculogenesis and angiogenesis. Trends Cardiovas Med. 2004 Nov 1;14(8):308-13. doi: 10.1016/j.tcm.2004.09.003
Gonzalez AC, Ferreira M, Ariel T, Reis SR, Andrade Z, Peixoto Medrado A. Immunohistochemical evaluation of hedgehog signaling in epithelial/mesenchymal interactions in squamous cell carcinoma transformation: a pilot study. J Oral Pathol Med. 2016 Mar;45(3):173-9. doi:10.1111/jop.12346
Bielefeld KA, Amini-Nik S, Alman BA. Cutaneous wound healing: recruiting developmental pathways for regeneration. Cellular and Molecular Life Sciences. 2013 Jun 1;70(12):2059-81.
Gál P, Vidinský B, Toporcer T, Mokrý M, Mozeš Š, Longauer F, Sabo J. Histological assessment of the effect of laser irradiation on skin wound healing in rats. Photomed Laser Surg. 2006 Aug 1;24(4):480-8. doi:10.1089/pho.2006.24.480
Medrado AR, Pugliese LS, Reis SR, Andrade ZA. Influence of low-level laser therapy on wound healing and its biological action upon myofibroblasts. Laser Surg Med. 2003 Mar;32(3):239-44. doi:10.1002/lsm.10126
Medrado A, Costa T, Prado T, Reis S, Andrade Z. Phenotype characterization of pericytes during tissue repair following low‐level laser therapy. Photodermatology, photoimmunology & photomedicine. 2010 Aug;26(4):192-7. doi: 10.1111/j.1600-0781.2010.00521.x
Catao MHCV. The benefits of low-intensity laser in dental practice and stomatology. Rev Bras Patol Oral 2004; 3:214–218. [In Portuguese]
Barbul AD, Breslin RJ, Woodyard JP, Wasserkrug HL, Efron GE. The effect of in vivo T helper and T suppressor lymphocyte depletion on wound healing. Ann Surg. 1989 Apr;209(4):479-483.
Boyce DE, Jones WD, Ruge F, Harding KG, Moore K. The role of lymphocytes in human dermal wound healing. Br. J. Dermatol. 2000 Jul;143(1):59-65. doi:10.1046/j.1365-2133.2000.03591.x
Souza NH, Ferrari RA, Silva DF, Nunes FD, Bussadori SK, Fernandes KP. Effect of low-level laser therapy on the modulation of mitochondrial activity of macrophages. Braz J Phys Ther 2014;18(40):308–314. doi:10.1590/bjpt-rbf.2014.0046
Houreld NN, Ayuk SM, Abrahamse H. Expression of genes in normal fibroblasts cells (WS1) in response to irradiation at 660 nm. J Photochem Photobio B: Bio 2014; 130:146–152. doi:10.1016/j.jphotobiol.2013.11.018
Cherng S, Young J, Ma H. Alpha-smooth muscle actin (α-SMA). J Am Sci. 2008;4(4):7-9.
Andrade ZA. A double and paradoxical role for angiogenesis. Rev Patol Trop. 2013;42(3): 259–264.
Tazima MFGS, Vicente YAMV, Moriya T. Biology, and Wound Healing. Simp Fund Clín Cir 2008;4(3):259–264. [In Portuguese]
Lee JS, Semela D, Iredale J, Shah VH. Sinusoidal remodeling and angiogenesis: a new function for the liver-specific pericyte. J Hepatol. 2007; 45:817–825. doi: 10.1002/hep.21564
Athar M, Tang X, Lee JL, Kopelovich L, Kim AL. Hedgehog signaling in skin development and cancer. Experim Dermato. 2006; 15:667–677. doi: 10.1111/j.1600-0625.2006.00473.x
Sicklick JK, Li YX, Jayaraman A, Kannangai R, Qi Y, Vivekanandan P, Ludlow JW, Si, et al. Dysregulation of the Hedgehog pathway in human hepatocarcinogenesis. Carcicogenesis 2005;27(4):748-757. doi: 10.1093/carcin/bgi292
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