Q-switched 1064-nm dymium-doped yttrium aluminum garnet laser irradiation induces skin collagen synthesis by stimulating MAPKs pathway

  • Zhi Yang
  • Huiyi Xiang
  • Xiaoxia Duan
  • Jianmeng Liu
  • Xiaolin He
  • Yunting He
  • Shaoyu Hu
  • Li HeEmail author
Original Article


The 1064-nm Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG) laser is widely used in clinical practice. However, the effects of 1064-nm Q-switched Nd:YAG laser on skin collagen generation have not been fully elucidated. The objectives of the present study were to investigate whether the 1064-nm Q-switched Nd:YAG laser can be used for non-ablative rejuvenation and to explore the possible mechanism underlying the effects. Six-week-old SKH-1 hairless mice were irradiated by the 1064-nm Nd:YAG laser at fluences of 0, 0.5, 1, 1.5, and 2 J/cm2, respectively. The contents of hydroxyproline and hydration were detected after laser irradiation. Moreover, hematoxylin-eosin (HE) staining was preformed to evaluate the dermal thickness. Immunofluorescence was used to detect the expressions of MMP-2 and TIMP-1 in the skin after laser irradiation. Furthermore, qRT-PCR was performed to determine the expressions of TGF-β1 and Smad3. In addition, the expressions of ERK1/2, p-ERK1/2, p38, p-p38, JNK, ERK5, and collagen were evaluated by Western blotting. The results indicated that the levels of hydroxyproline, hydration, and collagen were markedly increased; both the thickness of dermal was enhanced after low dose of laser treatment. Moreover, the expression of TIMP-1 was significantly increased, whereas the expression of MMP-2 was remarkably decreased after laser irradiation. Meanwhile, TGF-β1, Smad3, p-ERK1/2, p-P38, and JNK productions were significantly enhanced in irradiated group compared with the ones non-irradiated. Nevertheless, no significant changes were observed in the expression of ERK5 after irradiation. In summary, our study demonstrated that Q-switched 1064-nm Nd:YAG laser can induce collagen generation, at least in part, through activating TGF-β1/Smad3/MAPK signaling pathway.


1064-nm Q-switched neodymium-doped yttrium aluminum garnet laser Collagen MAPKs ERK1/2 p38MAPK 


Funding information

This work was performed in Department of Dermatology, the first affiliated hospital of Kunming medical university and supported by the National Natural Science Foundation of China (81560507) and the Yunnan Provincial Department of Science and Technology-Kunming Medical University Joint Research Fund for Applied Basic Research (2014FB023).

Compliance with ethical standards

Conflict of interest

This authors declare that they have no conflict of interest.

Ethical approval

This study received ethical approval from the first affiliated hospital of Kunming medical university ethics committee (approval no. 2017-06).


  1. 1.
    Farage MA, Miller KW, Elsner P, Maibach HI (2013) Characteristics of the aging skin. Adv Wound Care (New Rochelle) 2:5–10CrossRefGoogle Scholar
  2. 2.
    Tao L, Wu J, Qian H, Lu Z, Li Y, Wang W, Zhao X, Tu P, Yin R, Xiang L (2015) Intense pulsed light, near infrared pulsed light, and fractional laser combination therapy for skin rejuvenation in Asian subjects: a prospective multi-center study in China. Lasers Med Sci 30:1977–1983CrossRefGoogle Scholar
  3. 3.
    Yaar M, Gilchrest BA (2007) Photoaging: mechanism, prevention and therapy. Br J Dermatol 57:874–887CrossRefGoogle Scholar
  4. 4.
    Goldberg DJ, Silapunt S (2001) Histologic evaluation of a Q-switched Nd: YAG laser in the nonablative treatment of wrinkles. Dermatol Surg 27:744–746PubMedGoogle Scholar
  5. 5.
    Zhou ZQ, Yang RY (2015) Clinical progresses on non-surgical facial rejuvenation. J Pract Dermatol 8:438–444Google Scholar
  6. 6.
    Goldberg DJ, Metzler C (1999) Skin resurfacing utilizing a lowfluence Nd: YAG laser. J Cut laser Ther 1:23–27CrossRefGoogle Scholar
  7. 7.
    do Rhee Y, Cho HI, Park GH, Moon HR, Chang SE, Won CH, Jung JM, Park KY, Lee MW, Choi JH, Moon KC, Lee DC, Goo B (2016) Histological and molecular analysis of the long-pulse 1064-nm Nd: YAG laser on irradiation the ultraviolet-damaged skin of hairless mice: In association with pulse duration change. J Cosmet Laser Ther 18:16–21Google Scholar
  8. 8.
    Dang YY, Liu B, Liu LX, Ye XY, Bi XL, Zhang Y, Gu J (2011) The 800-nm diode laser irradiation induces skin collagen synthesis by stimulating TGF-β/Smad signaling pathway. Lasers Med Sci 26:837–843CrossRefGoogle Scholar
  9. 9.
    Huang JH, Luo X, Lu JY, Chen J, Zuo CX, Xiang YP, Yang SB, Tan L, Kang J, Bi ZG (2011) IPL irradiation rejuvenates skin collagen via the bidirectional regulation of MMP-1 and TGF-β1 mediated by MAPKs in fibroblasts. Lasers Med Sci 26:381–387CrossRefGoogle Scholar
  10. 10.
    Yang B, Ji C, Kang J, Chen W, Bi Z, Wan Y (2009) Trans-zeatin inhibits UVB-induced matrix metalloproteinase-1 expression via MAP kinase signaling in human skin fibroblasts. Int J Mol Med 23:555–560CrossRefGoogle Scholar
  11. 11.
    Kocic H, Arsic I, Stankovic M, Tiodorovic D, Ciric V, Kocic G (2017) Proliferative, anti-apoptotic and immune-enhancing effects of L-arginine in culture of skin fibroblasts. J Biol Regul Homeost Agents 31:667–672PubMedGoogle Scholar
  12. 12.
    Ryu AR, Lee MY (2017) Chlorin e6-mediated photodynamic therapy promotes collagen production and suppresses MMPs expression via modulating AP-1 signaling in P. acnes-stimulated HaCaT cells. Photodiagn Photodyn Ther 20:71–77CrossRefGoogle Scholar
  13. 13.
    Kunimatsu R, Gunji H, Tsuka Y, Yoshimi Y, Awada T, Sumi K, Nakajima K, Kimura A, Hiraki T, Abe T, Naoto H, Yanoshita M, Tanimoto K (2018) Effects of high-frequency near-infrared diode laser irradiation on the proliferation and migration of mouse calvarial osteoblasts. Lasers Med Sci 33: 959–966CrossRefGoogle Scholar
  14. 14.
    Shin MK, Lee JH, Lee SJ, Kim NI (2012) Platelet-rich plasma combined with fractional laser therapy for skin rejuvenation. Dermatol Surg 38:623–630CrossRefGoogle Scholar
  15. 15.
    Li ZQ, Zhuang L, Feng ZC, Qi QC, Zhong H, Ma WY (2013) Analysis of the endoplasmic reticulum stress in non-ablative skin rejuvenation using Q-switched 1064 nm Nd: YAG laser. Chin J Plast Surg 29:113–116 (in Chinese)Google Scholar
  16. 16.
    Chan HH, Lam LK, Wong DS, Wei WI (2003) Role of skin cooling in improving pateint tolerability of Q-switched alexandrite (QS Alex) laser in nevus of Ota treatment. Lasers Surg Med 32:148–151CrossRefGoogle Scholar
  17. 17.
    Nikolaou VA, Stratigos AJ, Dover JS (2005) Nonablative skin rejuvenation. J Cosmet Dermatol 4:301–307CrossRefGoogle Scholar
  18. 18.
    Oh J, Kim N, Seo S, Kim IH (2010) Alteration of extracellular matrix modulators after nonablative laser therapy in skin rejuvenation. Br J Dermatol 157:306–310CrossRefGoogle Scholar
  19. 19.
    Cao Y, Huo R, Feng Y, Li Q, Wang F (2011) Effects of intense pulsed light on the biological properties and ultrastructure of skin dermal fibroblasts: potential roles in photoaging. Photomed Laser Surg 29:327–332CrossRefGoogle Scholar
  20. 20.
    Alster T (2003) Laser scar revision: comparison study of 585-nm pulsed dye laser with and without intralesional corticosteroids. Dermatol Surg 29:25–29PubMedGoogle Scholar
  21. 21.
    Hinz B (2007) Formation and function of the myofibroblast during tissue repair. J Invest Dermatol 127:526–537CrossRefGoogle Scholar
  22. 22.
    Dang Y, Ye X, Weng Y, Tong Z, Ren Q (2010) Effects of the 532-nm and 1064-nm Q-switched Nd:YAG lasers on collagen turnover of cultured human skin fibroblasts: a comparative study. Lasers Med Sci 25:719–726CrossRefGoogle Scholar
  23. 23.
    Nishimoto S, Nishida E (2006) MAPK signalling: ERK5 versus ERK1/2. EMBO Rep 7:782–786CrossRefGoogle Scholar
  24. 24.
    Brennan M, Bhatti H, Nerusu KC, Bhagavathula N, Kang S, Fisher GJ, Varani J, Voorhees JJ (2003) Matrix metalloproteinase-1 is the major collagenolytic enzyme responsible for collagen damage in UVirradiated human skin. Photochem Photobiol 78:43–48CrossRefGoogle Scholar
  25. 25.
    Gomes LR, Terra LF, Wailemann RA, Labriola L, Sogayar MC (2012) TGF-β1 modulates the homeostasis between MMPs and MMP inhibitors through p38 MAPK and ERK1/2 in highly invasive breast cancer cells. BMC Cancer 12:26CrossRefGoogle Scholar
  26. 26.
    Lin X, Duan X, Liang YY, Su Y, Wrighton KH, Long J, Hu M, Davis CM, Wang J, Brunicardi FC, Shi Y, Chen YG, Meng A, Feng XH (2006) PPM1A functions as a Smad phosphatase to terminate TGFβ Signalin. Cell 125:915–928CrossRefGoogle Scholar
  27. 27.
    Lake D, Corrêa SA, Müller J (2016) Negative feedback regulation of the ERK1/2 MAPK pathway. Cell Mol Life Sci 73:4397–4413CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Department of DermatologyThe first affiliated hospital of Kunming medical UniversityKunmingChina

Personalised recommendations