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Far infrared promotes wound healing through activation of Notch1 signaling

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Abstract

The Notch signaling pathway is critically involved in cell proliferation, differentiation, development, and homeostasis. Far infrared (FIR) has an effect that promotes wound healing. However, the underlying molecular mechanisms are unclear. In the present study, we employed in vivo and HaCaT (a human skin keratinocyte cell line) models to elucidate the role of Notch1 signaling in FIR-promoted wound healing. We found that FIR enhanced keratinocyte migration and proliferation. FIR induced the Notch1 signaling pathway in HaCaT cells and in a microarray dataset from the Gene Expression Omnibus database. We next determined the mRNA levels of NOTCH1 in paired normal and wound skin tissues derived from clinical patients using the microarray dataset and Ingenuity Pathway Analysis software. The result indicated that the Notch1/Twist1 axis plays important roles in wound healing and tissue repair. In addition, inhibiting Notch1 signaling decreased the FIR-enhanced proliferation and migration. In a full-thickness wound model in rats, the wounds healed more rapidly and the scar size was smaller in the FIR group than in the light group. Moreover, FIR could increase Notch1 and Delta1 in skin tissues. The activation of Notch1 signaling may be considered as a possible mechanism for the promoting effect of FIR on wound healing. FIR stimulates keratinocyte migration and proliferation. Notch1 in keratinocytes has an essential role in FIR-induced migration and proliferation. NOTCH1 promotes TWIST1-mediated gene expression to assist wound healing. FIR might promote skin wound healing in a rat model.

Key messages

  • FIR stimulates keratinocyte migration and proliferation.

  • Notch1 in keratinocytes has an essential role in FIR-induced migration and proliferation.

  • NOTCH1 promotes TWIST1-mediated gene expression to assist wound healing.

  • FIR might promote skin wound healing in a rat model.

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References

  1. Toyokawa H, Matsui Y, Uhara J, Tsuchiya H, Teshima S, Nakanishi H, Kwon AH, Azuma Y, Nagaoka T, Ogawa T et al (2003) Promotive effects of far-infrared ray on full-thickness skin wound healing in rats. Exp Biol Med (Maywood, NJ) 228:724–729

    Article  CAS  Google Scholar 

  2. Martin P (1997) Wound healing—aiming for perfect skin regeneration. Science 276:75–81

    Article  CAS  PubMed  Google Scholar 

  3. Nagato H, Umebayashi Y, Wako M, Tabata Y, Manabe M (2006) Collagen-poly glycolic acid hybrid matrix with basic fibroblast growth factor accelerated angiogenesis and granulation tissue formation in diabetic mice. J Dermatol 33:670–675

    Article  CAS  PubMed  Google Scholar 

  4. Bielefeld KA, Amini-Nik S, Alman BA (2013) Cutaneous wound healing: recruiting developmental pathways for regeneration. Cell Mol Life Sci 70:2059–2081

    Article  CAS  PubMed  Google Scholar 

  5. Okuyama R, Tagami H, Aiba S (2008) Notch signaling: its role in epidermal homeostasis and in the pathogenesis of skin diseases. J Dermatol Sci 49:187–194

    Article  PubMed  Google Scholar 

  6. Gridley T (2010) Notch signaling in the vasculature. Curr Top Dev Biol 92:277–309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm JS, Schroeter EH, Schrijvers V, Wolfe MS, Ray WJ et al (1999) A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398:518–522

    Article  PubMed  Google Scholar 

  8. Takeshita K, Satoh M, Ii M, Silver M, Limbourg FP, Mukai Y, Rikitake Y, Radtke F, Gridley T, Losordo DW et al (2007) Critical role of endothelial Notch1 signaling in postnatal angiogenesis. Circ Res 100:70–78

    Article  CAS  PubMed  Google Scholar 

  9. Tang D, Yan T, Zhang J, Jiang X, Zhang D, Huang Y (2017) Notch1 signaling contributes to hypoxia-induced high expression of integrin beta1 in keratinocyte migration. Sci Rep 7:43926

    Article  PubMed  PubMed Central  Google Scholar 

  10. Tsai SR, Hamblin MR (2017) Biological effects and medical applications of infrared radiation. J Photochem Photobiology B 170:197–207

    Article  CAS  Google Scholar 

  11. Anders JJ, Lanzafame RJ, Arany PR (2015) Low-level light/laser therapy versus photobiomodulation therapy. Photomed Laser Surg 33:183–184

    Article  PubMed  PubMed Central  Google Scholar 

  12. Chiu HW, Chen CH, Chang JN, Chen CH, Hsu YH (2016) Far-infrared promotes burn wound healing by suppressing NLRP3 inflammasome caused by enhanced autophagy. J Mol Med (Berlin, Germany) 94:809–819

    Article  CAS  Google Scholar 

  13. Chiu HW, Chen CH, Chen YJ, Hsu YH (2017) Far-infrared suppresses skin photoaging in ultraviolet B-exposed fibroblasts and hairless mice. PLoS One 12:e0174042

    Article  PubMed  PubMed Central  Google Scholar 

  14. Chen CH, Chen TH, Wu MY, Chou TC, Chen JR, Wei MJ, Lee SL, Hong LY, Zheng CM, Chiu IJ et al (2017) Far-infrared protects vascular endothelial cells from advanced glycation end products-induced injury via PLZF-mediated autophagy in diabetic mice. Sci Rep 7:40442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chiu HW, Ho SY, Guo HR, Wang YJ (2009) Combination treatment with arsenic trioxide and irradiation enhances autophagic effects in U118-MG cells through increased mitotic arrest and regulation of PI3K/Akt and ERK1/2 signaling pathways. Autophagy 5:472–483

    Article  CAS  PubMed  Google Scholar 

  16. Margadant C, Raymond K, Kreft M, Sachs N, Janssen H, Sonnenberg A (2009) Integrin alpha3beta1 inhibits directional migration and wound re-epithelialization in the skin. J Cell Sci 122:278–288

    Article  CAS  PubMed  Google Scholar 

  17. Inoue S, Kabaya M (1989) Biological activities caused by far-infrared radiation. Int J Biometeorol 33:145–150

    Article  CAS  PubMed  Google Scholar 

  18. Sommer AP, Zhu D, Mester AR, Forsterling HD (2011) Pulsed laser light forces cancer cells to absorb anticancer drugs—the role of water in nanomedicine. Artif Cells Blood Substit Immobil Biotechnol 39:169–173

    Article  CAS  PubMed  Google Scholar 

  19. Sommer AP, Caron A, Fecht HJ (2008) Tuning nanoscopic water layers on hydrophobic and hydrophilic surfaces with laser light. Langmuir 24:635–636

    Article  CAS  PubMed  Google Scholar 

  20. Ravna AW, Sylte I (2012) Homology modeling of transporter proteins (carriers and ion channels). Methods Mol Biol (Clifton, NJ) 857:281–299

    Article  CAS  Google Scholar 

  21. Vatansever F, Hamblin MR (2012) Far infrared radiation (FIR): its biological effects and medical applications. Photonics Lasers Med 4:255–266

    PubMed  PubMed Central  Google Scholar 

  22. Mohd Hilmi AB, Halim AS, Jaafar H, Asiah AB, Hassan A (2013) Chitosan dermal substitute and chitosan skin substitute contribute to accelerated full-thickness wound healing in irradiated rats. Biomed Res Int 2013:795458

    Article  PubMed  PubMed Central  Google Scholar 

  23. Clark RA (1985) Cutaneous tissue repair: basic biologic considerations. I J Am Acad Dermatol 13:701–725

    Article  CAS  PubMed  Google Scholar 

  24. Ranganathan P, Weaver KL, Capobianco AJ (2011) Notch signalling in solid tumours: a little bit of everything but not all the time. Nat Rev Cancer 11:338–351

    Article  CAS  PubMed  Google Scholar 

  25. Shi Y, Shu B, Yang R, Xu Y, Xing B, Liu J, Chen L, Qi S, Liu X, Wang P et al (2015) Wnt and Notch signaling pathway involved in wound healing by targeting c-Myc and Hes1 separately. Stem Cell Res Ther 6:120

    Article  PubMed  PubMed Central  Google Scholar 

  26. Shaw TJ, Martin P (2009) Wound repair at a glance. J Cell Sci 122:3209–3213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Chigurupati S, Arumugam TV, Son TG, Lathia JD, Jameel S, Mughal MR, Tang SC, Jo DG, Camandola S, Giunta M et al (2007) Involvement of notch signaling in wound healing. PLoS One 2:e1167

    Article  PubMed  PubMed Central  Google Scholar 

  28. Gao XJ, Liu JW, Zhang QG, Zhang JJ, Xu HT, Liu HJ (2015) Nobiletin inhibited hypoxia-induced epithelial-mesenchymal transition of lung cancer cells by inactivating of Notch-1 signaling and switching on miR-200b. Die Pharmazie 70:256–262

    CAS  PubMed  Google Scholar 

  29. Chen J, Yuan W, Wu L, Tang Q, Xia Q, Ji J, Liu Z, Ma Z, Zhou Z, Cheng Y et al (2017) PDGF-D promotes cell growth, aggressiveness, angiogenesis and EMT transformation of colorectal cancer by activation of Notch1/Twist1 pathway. Oncotarget 8:9961–9973

    PubMed  Google Scholar 

  30. Gupta A, Dai T, Hamblin MR (2014) Effect of red and near-infrared wavelengths on low-level laser (light) therapy-induced healing of partial-thickness dermal abrasion in mice. Lasers Med Sci 29:257–265

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported by the Taipei Medical University-Shuang Ho Hospital (106TMU-SHH-07).

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Correspondence to Hui-Wen Chiu.

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Hsu, YH., Lin, YF., Chen, CH. et al. Far infrared promotes wound healing through activation of Notch1 signaling. J Mol Med 95, 1203–1213 (2017). https://doi.org/10.1007/s00109-017-1580-y

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  • DOI: https://doi.org/10.1007/s00109-017-1580-y

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