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GATA3 inhibits proliferation and induces expression of both early and late differentiation markers in keratinocytes of the human epidermis

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Abstract

GATA3 belongs to the GATA transcription factor family and is a crucial regulator of lymphocyte differentiation. More recently, GATA3 was shown to be involved in skin cell lineage determination, in morphogenesis and maintenance of hair follicle keratinocytes as well as in epidermal barrier formation in mouse. In human, the potential role of GATA3 in the regulation of interfollicular epidermal homeostasis was still poorly explored. We thus investigated whether GATA3 could play a role in the regulation of proliferation and/or differentiation processes in human primary keratinocytes. We silenced the expression of GATA3 by small interfering RNA in either proliferating or differentiated human primary keratinocytes and analyzed the effect on cell proliferation and differentiation. We showed that GATA3 inhibition increased cell number, BrdU incorporation and expression of the proliferation markers PCNA and Ki67, demonstrating that GATA3 can inhibit keratinocyte proliferation. Moreover, GATA3 seems to be able to induce keratinocyte differentiation since its silencing leads to a decrease of both early and late differentiation markers such as Keratins 1 and 10, Involucrin and Loricrin. Our results demonstrate that GATA3 transcription factor inhibits proliferation and induces differentiation of primary keratinocytes, which suggest that it may regulate human interfollicular epidermal renewal.

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References

  1. Berthier-Vergnes O, El Kharbili M, de la Fouchardiere A, Pointecouteau T, Verrando P, Wierinckx A, Lachuer J, Le Naour F, Lamartine J (2011) Gene expression profiles of human melanoma cells with different invasive potential reveal TSPAN8 as a novel mediator of invasion. Br J Cancer 104(1):155–165

    Google Scholar 

  2. Boukamp P, Petrussevska RT, Breitkreutz D, Hornung J, Markham A, Fusenig NE (1988) Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J Cell Biol 106(3):761–771

    Article  CAS  PubMed  Google Scholar 

  3. Candi E, Terrinoni A, Rufini A, Chikh A, Lena AM, Suzuki Y, Sayan BS, Knight RA, Melino G (2006) p63 is upstream of IKK alpha in epidermal development. J Cell Sci 119(Pt 22):4617–4622

    Article  CAS  PubMed  Google Scholar 

  4. Cantor AB, Orkin SH (2002) Transcriptional regulation of erythropoiesis: an affair involving multiple partners. Oncogene 21(21):3368–3376

    Article  CAS  PubMed  Google Scholar 

  5. Chikh A, Sayan E, Thibaut S, Lena AM, DiGiorgi S, Bernard BA, Melino G, Candi E (2007) Expression of GATA-3 in epidermis and hair follicle: relationship to p63. Biochem Biophys Res Commun 361(1):1–6

    Article  CAS  PubMed  Google Scholar 

  6. de Guzman Strong C, Wertz PW, Wang C, Yang F, Meltzer PS, Andl T, Millar SE, Ho IC, Pai SY, Segre JA (2006) Lipid defect underlies selective skin barrier impairment of an epidermal-specific deletion of Gata-3. J Cell Biol 175(4):661–670

    Article  Google Scholar 

  7. Descargues P, Sil AK, Karin M (2008) IKK alpha, a critical regulator of epidermal differentiation and a suppressor of skin cancer. EMBO J 27(20):2639–2647

    Article  CAS  PubMed  Google Scholar 

  8. George KM, Leonard MW, Roth ME, Lieuw KH, Kioussis D, Grosveld F, Engel JD (1994) Embryonic expression and cloning of the murine GATA-3 gene. Development 120(9):2673–2686

    CAS  PubMed  Google Scholar 

  9. Grote D, Boualia SK, Souabni A, Merkel C, Chi X, Costantini F, Carroll T, Bouchard M (2008) Gata3 acts downstream of beta-catenin signaling to prevent ectopic metanephric kidney induction. PLoS Genet 4(12):e1000316

    Article  PubMed Central  PubMed  Google Scholar 

  10. Ho IC, Tai TS, Pai SY (2009) GATA3 and the T-cell lineage: essential functions before and after T-helper-2-cell differentiation. Nat Rev Immunol 9(2):125–135

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Kaufman CK, Zhou P, Pasolli HA, Rendl M, Bolotin D, Lim KC, Dai X, Alegre ML, Fuchs E (2003) GATA-3: an unexpected regulator of cell lineage determination in skin. Genes Dev 17(17):2108–2122

    Article  CAS  PubMed  Google Scholar 

  12. Kawachi Y, Ishitsuka Y, Maruyama H, Fujisawa Y, Furuta J, Nakamura Y, Otsuka F (2012) GATA-3 regulates differentiation-specific loricrin gene expression in keratinocytes. Exp Dermatol 21(11):859–864

    Article  CAS  PubMed  Google Scholar 

  13. Koster MI, Roop DR (2004) p63 and epithelial appendage development. Differentiation 72(8):364–370

    Article  CAS  PubMed  Google Scholar 

  14. Ku CJ, Hosoya T, Maillard I, Engel JD (2012) GATA-3 regulates hematopoietic stem cell maintenance and cell-cycle entry. Blood 119(10):2242–2251

    Article  CAS  PubMed  Google Scholar 

  15. Kuo CT, Leiden JM (1999) Transcriptional regulation of T lymphocyte development and function. Annu Rev Immunol 17:149–187

    Article  CAS  PubMed  Google Scholar 

  16. Kurek D, Garinis GA, van Doorninck JH, van der Wees J, Grosveld FG (2007) Transcriptome and phenotypic analysis reveals Gata3-dependent signalling pathways in murine hair follicles. Development 134(2):261–272

    Article  CAS  PubMed  Google Scholar 

  17. Masse I, Barbollat-Boutrand L, Molina M, Berthier-Vergnes O, Joly-Tonetti N, Martin MT, de Fromentel CC, Kanitakis J, Lamartine J (2012) Functional interplay between p63 and p53 controls RUNX1 function in the transition from proliferation to differentiation in human keratinocytes. Cell Death Dis 3:e318

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Mills AA, Zheng B, Wang XJ, Vogel H, Roop DR, Bradley A (1999) p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature 398(6729):708–713

    Article  CAS  PubMed  Google Scholar 

  19. Pandolfi PP, Roth ME, Karis A, Leonard MW, Dzierzak E, Grosveld FG, Engel JD, Lindenbaum MH (1995) Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal liver haematopoiesis. Nat Genet 11(1):40–44

    Article  CAS  PubMed  Google Scholar 

  20. Racz E, Kurek D, Kant M, Baerveldt EM, Florencia E, Mourits S, de Ridder D, Laman JD, van der Fits L, Prens EP (2011) GATA3 expression is decreased in psoriasis and during epidermal regeneration; induction by narrow-band UVB and IL-4. PLoS One 6(5):e19806

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Sellheyer K, Krahl D (2010) Expression pattern of GATA-3 in embryonic and fetal human skin suggests a role in epidermal and follicular morphogenesis. J Cutan Pathol 37(3):357–361

    Article  PubMed  Google Scholar 

  22. Son do N, Li L, Katsuyama H, Komatsu N, Saito M, Tanii H, Saijoh K (2009) Abundant expression of Kallikrein 1 gene in human keratinocytes was mediated by GATA3. Gene 436(1–2):121–127

    Article  PubMed  Google Scholar 

  23. Truong AB, Kretz M, Ridky TW, Kimmel R, Khavari PA (2006) p63 regulates proliferation and differentiation of developmentally mature keratinocytes. Genes Dev 20(22):3185–3197

    Article  CAS  PubMed  Google Scholar 

  24. Tsarovina K, Reiff T, Stubbusch J, Kurek D, Grosveld FG, Parlato R, Schutz G, Rohrer H (2010) The Gata3 transcription factor is required for the survival of embryonic and adult sympathetic neurons. J Neurosci 30(32):10833–10843

    Article  CAS  PubMed  Google Scholar 

  25. Tschachler E (2007) Psoriasis: the epidermal component. Clin Dermatol 25(6):589–595

    Article  PubMed  Google Scholar 

  26. van der Wees J, van Looij MA, de Ruiter MM, Elias H, van der Burg H, Liem SS, Kurek D, Engel JD, Karis A, van Zanten BG, de Zeeuw CI, Grosveld FG, van Doorninck JH (2004) Hearing loss following Gata3 haploinsufficiency is caused by cochlear disorder. Neurobiol Dis 16(1):169–178

    Article  PubMed  Google Scholar 

  27. Yang A, Schweitzer R, Sun D, Kaghad M, Walker N, Bronson RT, Tabin C, Sharpe A, Caput D, Crum C, McKeon F (1999) p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature 398(6729):714–718

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Dr. Clavel (Service d’Urologie, Clinique du Tonkin, Villeurbanne, France) for skin biopsies, Dr. Kanitakis (Department of Dermatology, Edouard Herriot Hospital, Lyon, France) for normal human skin sections, Sarah Bilodeau for technical assistance and the ANIPATH platform for immunohistochemical processing. This work was supported by a grant from the French Society for Dermatological Research (SRD).

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Authors and Affiliations

  1. Université de Lyon, 69003, Lyon, France

    Ingrid Masse, Laetitia Barbollat-Boutrand, Manale El Kharbili, Odile Berthier-Vergnes, Damien Aubert & Jérôme Lamartine

  2. Université Lyon 1, 69003, Lyon, France

    Ingrid Masse, Laetitia Barbollat-Boutrand, Manale El Kharbili, Odile Berthier-Vergnes, Damien Aubert & Jérôme Lamartine

  3. Centre de Génétique et de Physiologie Moléculaires et Cellulaires, CNRS UMR5534–Université Lyon I, 43 Bd du 11 Novembre 1918, 69622, Villeurbanne Cedex, France

    Ingrid Masse, Laetitia Barbollat-Boutrand, Manale El Kharbili, Odile Berthier-Vergnes, Damien Aubert & Jérôme Lamartine

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  1. Ingrid Masse
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  2. Laetitia Barbollat-Boutrand
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Correspondence to Ingrid Masse.

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Masse, I., Barbollat-Boutrand, L., Kharbili, M.E. et al. GATA3 inhibits proliferation and induces expression of both early and late differentiation markers in keratinocytes of the human epidermis. Arch Dermatol Res 306, 201–208 (2014). https://doi.org/10.1007/s00403-013-1435-5

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  • DOI: https://doi.org/10.1007/s00403-013-1435-5

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