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Cell proliferation and migration mechanism of caffeoylserotonin and serotonin via serotonin 2B receptor in human keratinocyte HaCaT cells

  • Kim, Hye-Eun (Department of Oral Pathology, Dental Science Research Institute and Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University) ;
  • Cho, Hyejoung (Department of Oral Pathology, Dental Science Research Institute and Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University) ;
  • Ishihara, Atsushi (Faculty of Agriculture, Tottori University) ;
  • Kim, Byungkuk (Department of Oral Pathology, Dental Science Research Institute and Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University) ;
  • Kim, Okjoon (Department of Oral Pathology, Dental Science Research Institute and Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University)
  • Received : 2017.10.31
  • Accepted : 2018.01.05
  • Published : 2018.04.30

Abstract

Caffeoylserotonin (CaS), one derivative of serotonin (5-HT), is a secondary metabolite produced in pepper fruits with strong antioxidant activities. In this study, we investigated the effect of CaS on proliferation and migration of human keratinocyte HaCaT cells compared to that of 5-HT. CaS enhanced keratinocyte proliferation even under serum deficient condition. This effect of CaS was mediated by serotonin 2B receptor (5-HT2BR) related to the cell proliferation effect of 5-HT. We also confirmed that both CaS and 5-HT induced G1 progression via 5-HT2BR/ERK pathway in HaCaT cells. However, Akt pathway was additionally involved in upregulated expression levels of cyclin D1 and cyclin E induced by CaS by activating 5-HT2BR. Moreover, CaS and 5-HT induced cell migration in HaCaT cells via 5-HT2BR. However, 5-HT regulated cell migration only through ERK/AP-1/MMP9 pathway while additional Akt/NF-${\kappa}B$/MMP9 pathway was involved in the cell migration effect of CaS. These results suggest that CaS can enhance keratinocyte proliferation and migration. It might have potential as a reagent beneficial for wound closing and cell regeneration.

Keywords

Caffeoylserotonin;Cell migration;G1 progression;Serotonin 2B receptor;Serotonin

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

References

  1. Kang K, Lee K, Ishihara A et al (2010) Induced synthesis of caffeoylserotonin in pepper fruits upon infection by the anthracnose fungus, Colletotrichum gloeosporioides. Sci Hortic 124, 290-293 https://doi.org/10.1016/j.scienta.2009.12.036
  2. Choi J, Kim H, Choi Y et al (2010) Cytoprotective activities of hydorxycinnamic acid amides of serotonin against oxidative stress-induced damage in HepG2 and HaCaT cells. Fitoterapia 81, 1134-1141 https://doi.org/10.1016/j.fitote.2010.07.015
  3. Nguyen C, Kim H and Lee S (2013) Caffeoylserotonin protects human keratinocyte HaCaT Cells against $H_2O_2$-induced oxidative stress and apoptosis through upregulation of HO-1 expression via activation of the PI3K/Akt/Nrf2 Pathway. Phytother Res 27, 1810-1818 https://doi.org/10.1002/ptr.4931
  4. Munz B, Frank S, Hubner G, Olsen E and Werner S (1997) Novel type of glutathione peroxidase: expression and regulation during wound repair. Biochem J 326, 579-585 https://doi.org/10.1042/bj3260579
  5. O'Toole E, Goel M and Woodley D (1996) Hydrogen peroxide inhibits human keratinocyte migration. Dermatol Surg 22, 525-529
  6. Cerutti P and Trump B (1991) Inflammation and oxidative stress in carcinogenesis. Cancer Cells 3, 1-7
  7. James T, Hughes M, Cherry G and Taylor R (2003) Evidence of oxidative stress in chronic venous ulcers. Wound Repair Regen 11, 172-176 https://doi.org/10.1046/j.1524-475X.2003.11304.x
  8. Musalmah M, Nizrana M, Fairuz A et al (2005) Comparative effects of palm vitamin e and alpha- tocopherol on healing and wound tissue antioxidant enzyme levels in diabetic rats. Lipids 40, 575-580 https://doi.org/10.1007/s11745-005-1418-9
  9. Senel O, Cetinkale O, Ozbay G, Ahcioglu F and Bulan R (1997) Oxygen free radicals impair wound healing in ischemic rat skin. Ann Plast Surg 39, 516-523 https://doi.org/10.1097/00000637-199711000-00012
  10. Masaki H (2010) Role of antioxidants in the skin: Anti-aging effects. J Dermatol Sci 58, 85-90 https://doi.org/10.1016/j.jdermsci.2010.03.003
  11. Nebigil C, Launay J, Hickel P, Toursnois C and Maroteaux L (2000) 5-hydroxytryptamine 2B receptor regulates cell-cycle progression: cross-talk with tyrosine kinase pathways. Proc Natl Acad Sci U S A 97, 2591-2596 https://doi.org/10.1073/pnas.050282397
  12. Li B, Zhang S, Li M, Hertz L and Peng L (2010) Serotonin increases ERK1/2 phosphorylation in astrocytes by stimulation of 5-HT2B and 5-HT2C receptors. Neurochem Int 57, 432-439 https://doi.org/10.1016/j.neuint.2010.04.017
  13. Slominski A, Pisarchik A, Abytek B et al (2003) Functional activity of serotoninergic and melatoninergic systems expressed in the skin. J Cell Physiol 196, 144-153 https://doi.org/10.1002/jcp.10287
  14. Draetta G, Luca F, Westendorf J et al (1989) Cdc2 protein kinase is complexed with both cyclin A and B: evidence for proteolytic inactivation of MPF. Cell 56, 829-838 https://doi.org/10.1016/0092-8674(89)90687-9
  15. Ruhul Amin A, Senga T, Oo M, Thant A and Hamaguchi M (2003) Secretion of matrix metalloproteinase-9 by the proinflammatory cytokine, IL-$1{\beta}$: a role for the dual signaling pathways, Akt and Erk. Genes Cells 8, 515-523 https://doi.org/10.1046/j.1365-2443.2003.00652.x
  16. Kwak S, Park B, Kim H et al (2012) Association of variations in TPH1 and HTR2B with gestational weight gain and measures of obesity. Obesity (Silver Spring) 20, 233-238 https://doi.org/10.1038/oby.2011.253
  17. Naito K, Tanaka C, Mitsuhashi M et al (2016) Signal Transduction mechanism of serotonin 5-HT2B receptormediated DNA synthesis and proliferation in primary culture of adult rat hepatocytes. Bol Pharm Bull 39, 121-129 https://doi.org/10.1248/bpb.b15-00735
  18. Dai S, Yu L, Shi X et al (2014) Serotonin regulates osteoblast proliferation and function in vitro. Braz J Med Biol Res 47, 759-765 https://doi.org/10.1590/1414-431X20143565
  19. Chang F, Lee J, Navolanic P et al (2003) Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy. Leukemia 17, 590-603 https://doi.org/10.1038/sj.leu.2402824
  20. Alan Diehl J, Cheng M, Roussel M, and Sherr C (1998) Glycogen synthase kinase-$3{\beta}$ regulates cyclin D1 proteolysis and subvelular localization. Genes Dev 12, 3499-3511 https://doi.org/10.1101/gad.12.22.3499
  21. Liu Y, Tian X, Mao G et al (2012) Peroxisome proliferatoractivated receptor-$\gamma$ ameliorates pulmonary arterial hypertension by inhibiting 5-hydroxytryptamine 2B receptor. Hypertension 16, 1471-1478
  22. Ebrahimkhani M, Oakley F, Murphy L et al (2011) Stimulating healthy tissue regeneration by targeting the 5-HT2B receptor in chronic liver disease. Nat Med 17, 1668-1674 https://doi.org/10.1038/nm.2490