Advertisement

Archives of Dermatological Research

, Volume 306, Issue 1, pp 59–66 | Cite as

Melanosome uptake is associated with the proliferation and differentiation of keratinocytes

  • Hye-In Choi
  • Kyung-Cheol Sohn
  • Dong-Kyun Hong
  • Young Lee
  • Chang Deok Kim
  • Tae-Jin Yoon
  • Jin Woon Park
  • Sunggyun Jung
  • Jeung-Hoon Lee
  • Young Ho LeeEmail author
Original Paper

Abstract

Melanosomes are synthesized in melanocytes and transferred to neighboring keratinocytes. However, the associations of melanosome uptake with the proliferation and differentiation of keratinocytes are not fully understood. We examined the associations of melanosome uptake with keratinocyte differentiation and proliferation. SV40T-transformed human epidermal keratinocytes (SV-HEKs) were treated with isolated melanosomes. The effects of melanosome uptake on the proliferation and differentiation of the keratinocytes were analyzed by Western blotting and flow cytometry. The relationship between melanosome uptake and keratinocyte differentiation status was verified by determining the melanin content in the cells. Melanosomes reduced the proliferation of SV-HEKs in a dose-dependent manner, but did not induce differentiation. Melanosome uptake was higher in differentiating keratinocytes compared to non-differentiating keratinocytes, and inhibited significantly by PAR-2 inhibitor. Melanosomes inhibit keratinocyte proliferation. Moreover, melanosome uptake is influenced by keratinocyte differentiation status, being highest in mid-stage differentiating keratinocytes in a PAR-2 dependent manner.

Keywords

Melanosome uptake Keratinocyte Differentiation Proliferation Melanocyte 

Notes

Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (NRF-2012R1A1A2A10038685).

References

  1. 1.
    Ando H, Niki Y, Ito M, Akiyama K, Matsui MS, Yarosh DB et al (2012) Melanosomes are transferred from melanocytes to keratinocytes through the processes of packaging, release, uptake, and dispersion. J Invest Dermatol 132:1222–1229PubMedCrossRefGoogle Scholar
  2. 2.
    Ando H, Niki Y, Yoshida M, Ito M, Akiyama K, Kim JH et al (2011) Involvement of pigment globules containing multiple melanosomes in the transfer of melanosomes from melanocytes to keratinocytes. Cell Logist 1:12–20PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Ando H, Niki Y, Yoshida M, Ito M, Akiyama K, Kim JH et al (2010) Keratinocytes in culture accumulate phagocytosed melanosomes in the perinuclear area. Pigment Cell Melanoma Res 23:129–133PubMedCrossRefGoogle Scholar
  4. 4.
    Babiarz-Magee L, Chen N, Seiberg M, Lin CB (2004) The expression and activation of protease-activated receptor-2 correlate with skin color. Pigment Cell Res 17:241–251PubMedCrossRefGoogle Scholar
  5. 5.
    Bohm SK, Kong W, Bromme D, Smeekens SP, Anderson DC, Connolly A et al (1996) Molecular cloning, expression and potential functions of the human proteinase-activated receptor-2. Biochem J 314:1009–1016PubMedGoogle Scholar
  6. 6.
    Boissy RE (2003) Melanosome transfer to and translocation in the keratinocyte. Exp Dermatol 12(Suppl 2):5–12PubMedCrossRefGoogle Scholar
  7. 7.
    Byers HR, Maheshwary S, Amodeo DM, Dykstra SG (2003) Role of cytoplasmic dynein in perinuclear aggregation of phagocytosed melanosomes and supranuclear melanin cap formation in human keratinocytes. J Invest Dermatol 121:813–820PubMedCrossRefGoogle Scholar
  8. 8.
    Cardinali G, Ceccarelli S, Kovacs D, Aspite N, Lotti LV, Torrisi MR et al (2005) Keratinocyte growth factor promotes melanosome transfer to keratinocytes. J Invest Dermatol 125:1190–1199PubMedCrossRefGoogle Scholar
  9. 9.
    Gibbs S, Murli S, De Boer G, Mulder A, Mommaas AM, Ponec M (2000) Melanosome capping of keratinocytes in pigmented reconstructed epidermis–effect of ultraviolet radiation and 3-isobutyl-1-methyl-xanthine on melanogenesis. Pigment Cell Res 13:458–466PubMedCrossRefGoogle Scholar
  10. 10.
    Hearing VJ (2005) Biogenesis of pigment granules: a sensitive way to regulate melanocyte function. J Dermatol Sci 37:3–14PubMedCrossRefGoogle Scholar
  11. 11.
    Imokawa G (2004) Autocrine and paracrine regulation of melanocytes in human skin and in pigmentary disorders. Pigment Cell Res 17:96–110PubMedCrossRefGoogle Scholar
  12. 12.
    Marks MS, Seabra MC (2001) The melanosome: membrane dynamics in black and white. Nat Rev Mol Biol 2:738–748CrossRefGoogle Scholar
  13. 13.
    Menon GK, Grayson S, Elias PM (1985) Ionic calcium reservoirs in mammalian epidermis: ultrastructural localization by ion-capture cytochemistry. J Invest Dermatol 84:508–512PubMedCrossRefGoogle Scholar
  14. 14.
    Paine C, Sharlow E, Liebel F, Eisinger M, Shapiro S, Seiberg M (2001) An alternative approach to depigmentation by soybean extracts via inhibition of the PAR-2 pathway. J Invest Dermatol 116:587–595PubMedCrossRefGoogle Scholar
  15. 15.
    Park HY, Kosmadaki M, Yaar M, Gilchrest BA (2009) Cellular mechanisms regulating human melanogenesis. Cell Mol Life Sci 66:1493–1506PubMedCrossRefGoogle Scholar
  16. 16.
    Seiberg M, Paine C, Sharlow E, Andrade-Gordon P, Costanzo M, Eisinger M et al (2000) The protease-activated receptor 2 regulates pigmentation via keratinocyte–melanocyte interactions. Exp Cell Res 254:25–32PubMedCrossRefGoogle Scholar
  17. 17.
    Seiberg M, Paine C, Sharlow E, Andrade-Gordon P, Costanzo M, Eisinger M et al (2000) Inhibition of melanosome transfer results in skin lightening. J Invest Dermatol 115:162–167PubMedCrossRefGoogle Scholar
  18. 18.
    Sharlow ER, Paine CS, Babiarz L, Eisinger M, Shapiro S, Seiberg M (2000) The protease-activated receptor-2 upregulates keratinocyte phagocytosis. J Cell Sci 113:3093–3101PubMedGoogle Scholar
  19. 19.
    Shi G, Sohn KC, Li Z, Choi DK, Park YM, Kim JH et al (2013) Expression and functional role of Sox9 in human epidermal keratinocytes. PLoS One 8:e54355PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Vancoillie G, Lambert J, Mulder A, Koerten HK, Mommaas AM, Van Oostveldt P et al (2000) Cytoplasmic dynein colocalizes with melanosomes in normal human melanocytes. Br J Dermatol 143:298–306PubMedCrossRefGoogle Scholar
  21. 21.
    Wafa LA, Cheng H, Rao MA, Nelson CC, Cox M, Hirst M et al (2003) Isolation and identification of L-dopa decarboxylase as a protein that binds to and enhances transcriptional activity of the androgen receptor using the repressed transactivator yeast two-hybrid system. Biochem J 375:373–383PubMedCrossRefGoogle Scholar
  22. 22.
    Yamaguchi Y, Hearing VJ (2009) Physiological factors that regulate skin pigmentation. BioFactors 35:193–199PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Yoon HK, Sohn KC, Lee JS, Kim YJ, Bhak J, Yang JM et al (2008) Prediction and evaluation of protein–protein interaction in keratinocyte differentiation. Biochem Bioph Res Commun 377:662–667CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Hye-In Choi
    • 1
  • Kyung-Cheol Sohn
    • 2
  • Dong-Kyun Hong
    • 2
  • Young Lee
    • 2
  • Chang Deok Kim
    • 2
  • Tae-Jin Yoon
    • 3
  • Jin Woon Park
    • 4
  • Sunggyun Jung
    • 5
  • Jeung-Hoon Lee
    • 2
  • Young Ho Lee
    • 1
    Email author
  1. 1.Department of Anatomy, School of MedicineChungnam National UniversityDaejeonKorea
  2. 2.Department of Dermatology, School of MedicineChungnam National UniversityDaejeonKorea
  3. 3.Department of Dermatology, School of MedicineGyeongsang National UniversityJinjuKorea
  4. 4.Seoul Neurology ClinicNonsanKorea
  5. 5.Department of Plastic SurgeryKonyang University HospitalDaejeonKorea

Personalised recommendations