The function and therapeutic potential of miR-146 family in the suppression of Type-2-cell-promoting environment in atopic dermatitis
Grantee: Ana Rebane, PhD, Head of the RNA Biology Research Group, Institute of Biomedicine and translational Medicine, University of Tartu
Amount: DKK 1,650,000
Grant category: Research grants in open competition
Atopic dermatitis (AD) develops because of skin barrier abnormalities leading to activation of keratinocytes (KCs) and development of Type-2-cell- mediated chronic skin inflammation.
While the initial molecular events leading to induction of Type-2-cell-promoting cytokines are not well defined, it has been suggested that activation of the NF-kB pathway in response to environmental and/or intrinsic factors in KCs may be at play.
Concurrently, microRNAs – in particular miR-146a and miR-146b (miR-146a/b) – which are post-transcriptional gene expression regulators modulating various biological processes, have been shown to have an anti-inflammatory function in KCs and in the chronic phase of skin inflammation in AD.
In this project, Dr Rebane hypothesizes that miR-146a/b might inhibit AD-promoting events in the skin as these microRNAs act by targeting multiple factors in the NF-κB pathway.
Dr Rebane aims to study this relation using tissue culture and murine models, and assess the therapeutic potential in the regulation of Type-2-cell-promoting cytokines in the development of AD. In addition, it is planned to describe the expression of miR-146a/b isoforms and novel AD associated miRNAs in the skin of AD patients with the aim of detection of novel therapeutic targets.