title: The organic osmolyte betaine induces keratin 2 expression in rat epidermal keratinocytes - A genome-wide study in UVB irradiated organotypic 3D cultures.
abstract: The moisturizing and potentially protective properties of the organic osmolyte betaine (trimethylglycine) have made it an attractive component for skin care products. Its wide use despite the lack of comprehensive studies addressing its specific effects in skin led us to characterize the molecular targets of betaine in keratinocytes and to explore, whether it modifies the effects of acute UVB exposure. Genome-wide expression analysis was performed on organotypic cultures of rat epidermal keratinocytes, treated either with betaine (10mM), UVB (30 mJ/cm(2)) or their combination. Results were verified with qRT-PCR, western blotting and immunohistochemistry. Additionally, cell proliferation and differentiation were analyzed. Among the 89 genes influenced by betaine, the differentiation marker keratin 2 showed the highest upregulation, which was also confirmed at protein level. Expression of Egr1, a transcription factor, and Purkinje cell protein 4, a regulator of Ca(2+)/calmodulin metabolism, also increased, while downregulated genes included several ion-channel components, such as Fxyd2. Bioinformatics analyses suggest that genes modulated by betaine are involved in DNA replication, might counteract UV-induced processes, and include many targets of transcription factors associated with cell proliferation and differentiation. Our results indicate that betaine controls unique gene expression pathways in keratinocytes, including some involved in differentiation.
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland. Electronic address: leena.rauhala@uef.fi.
authors.forename: Leena
authors.initials: L
authors.lastname: Rauhala
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Lasse
authors.initials: L
authors.lastname: Hämäläinen
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Dunlop
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Pehkonen
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Bart
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Maarit
authors.initials: M
authors.lastname: Kokkonen
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Tammi
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Raija
authors.initials: R
authors.lastname: Tammi
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Pasonen-Seppänen
mesh_terms: D000818:Animals; D001622:Betaine / Q000494:pharmacology*; D002460:Cell Line; D055106:Genome-Wide Association Study; D053557:Keratin-2 / Q000235:genetics*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014466:Ultraviolet Rays
chemical_list: D053557:Keratin-2; D012333:RNA, Messenger; D001622:Betaine
keywords: Betaine; Gene expression; Keratin 2; Keratinocyte; Microarray; UVB