期刊
JOURNAL OF INVESTIGATIVE DERMATOLOGY
卷 130, 期 1, 页码 124-134出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/jid.2009.294
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资金
- National Psoriasis Foundation
- Swedish Research Council
- Medical Research Council [K2008-74x-07133-21A]
- Karolinska Institutet
- Swedish Psoriasis Association (Psoriasisforbundet)
- Welander Finsens Foundations
- Tore Nilsons Foundation
- Konsul ThC Bergh Foundations
- Stockholm County Council
- Marie Curie Intra-European
Terminal differentiation of keratinocytes is a multistep process that requires a coordinated program of gene expression. We aimed to explore the possible involvement of a previously unreported class of non-coding RNA genes, microRNAs (miRNAs) in keratinocyte differentiation by using miRNA expression profiling. Out of 365 miRNAs tested, 7 showed significant change between keratinocytes cultured in low or high calcium concentration. The highest-ranked upregulated gene was miR-203, whose expression was significantly upregulated in response to calcium and other inducers of keratinocyte differentiation such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and vitamin D-3. Differentiation-induced upregulation of miR-203 expression was blocked by treatment with specific inhibitors of protein kinase C (PKC), GF109203X, and Ro31-8220. Moreover, our results showed that the activator protein-1 (AP-1) proteins c-Jun and JunB regulate miR-203 expression in keratinocytes. In contrast to inducers of keratinocyte differentiation, epidermal growth factor and keratinocyte growth factor suppressed miR-203 expression in keratinocytes below the basal level. Overexpression of miR-203 in keratinocytes resulted in enhanced differentiation, whereas inhibition of miR-203 suppressed calcium-induced terminal differentiation as judged by involucrin expression. These results suggest that upregulation of miR-203 in human keratinocytes is required for their differentiation and is dependent on the activation of the PKC/AP-1 pathway.
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