title: GATA3 inhibits proliferation and induces expression of both early and late differentiation markers in keratinocytes of the human epidermis.
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.
authors.affiliation: Université de Lyon, 69003, Lyon, France, ingrid.masse@univ-lyon1.fr.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Masse
authors.forename: Laetitia
authors.initials: L
authors.lastname: Barbollat-Boutrand
authors.forename: Manale El
authors.initials: ME
authors.lastname: Kharbili
authors.forename: Odile
authors.initials: O
authors.lastname: Berthier-Vergnes
authors.forename: Damien
authors.initials: D
authors.lastname: Aubert
authors.forename: Jérôme
authors.initials: J
authors.lastname: Lamartine
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D000078404:Epidermal Cells; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D053556:Keratin-1 / Q000235:genetics / Q000378:metabolism; D053550:Keratin-10 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000502:physiology*; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D015415:Biomarkers; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D053556:Keratin-1; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D018809:Proliferating Cell Nuclear Antigen; D011498:Protein Precursors; D034741:RNA, Small Interfering; C064554:loricrin; D053550:Keratin-10; C032253:involucrin