Nrf2 and miR-29s regulate desmosome function in keratinocytes
| Dates: | 11 November 2014 |
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| Times: | 13:00 - 14:00 |
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| What is it: | Seminar |
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| Organiser: | Faculty of Life Sciences |
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| Who is it for: | University staff, Current University students |
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| Speaker: | Svitlana Kurinna |
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This seminar is part of the Tissue Systems seminar series. miRNAs are small RNA molecules implicated in skin homeostasis and repair; however, very little is known about mechanisms that regulate expression and function of miRNAs in epidermis during normal differentiation and in skin pathology. Recently, our group had identified miR-29a and miR-29b as regulators of desmosome function in keratinocytes in vivo. Increase in miR-29s downregulted desmosomal cadherin Dsc2 and impaired formation of desmosomes. In vivo, enhanced expression of miR-29 and decreased Dsc2 levels were observed in the epidermis of mice with constitutively active Nrf2, which was accompanied by structural alterations of the epidermal desmosomes and impairments of the epidermal barrier. We identified two gene clusters encoding for miR-29s as novel direct targets of Nrf2 in the epidermis and found a molecular mechanism of transcriptional regulation of miR-29 genes. These mechanisms are conserved in human keratinocytes where Nrf2 activates MIR29AB1 gene, and DNA methylation silences MIR29B2C. These results identified a novel Nrf2-miR-29-Dsc2 axis controlling desmosome formation and cutaneous homeostasis. Expanding on the mechanisms of miR-29s upregulation in vivo will lead to the clinical use of miR-29 mimics and antagomiRs to control skin regeneration and disease.
Speaker
Svitlana Kurinna
Organisation: ETH Zurich
Travel and Contact Information
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Lecture Theatre
Michael Smith Building
Manchester
