MiRNAs control skin homeostasis through post-transcriptional gene
repression by binding to their target mRNAs. However, their role in regulation
of apoptosis and hair loss in alopecia areata (AA) is largely unknown, which
became the aim of this study.
In AA mouse model (C3H/HeJ), global miRNA profiling revealed 22 miRNAs
with significant changes in their expression in AA affected skin. Amongst
these miRNAs, miR-486-5p was dramatically decreased in alopecic skin in
both humans and mice, in striking contrast to its prominent expression in the
hair follicle (HF) epithelium of healthy anagen skin. Moreover, the expression
of both pri-miR-486 and miR-486 is down-regulated in the human anagen
HFs and keratinocytes treated with IFN-g, one of the key factors contributing
to the immune privilege (IP) collapse in HFs.
Intradermal delivery of miR-486-5p mimic into mouse skin affected by AA
prevented premature entrance of HFs into catagen phase and reduced the
numbers of CD4+ and CD8+ lymphocytes in the peri- and intra-follicular skin
compartments. Consistently, subcutaneous administration of miR-486-5p
inhibitor delayed anagen progression associated with a higher number of
intrafollicular NKG2D+ cells in C3H/HeJ mice. Silencing of miR-486-5p in
human anagen HFs ex vivo caused premature catagen development and led
to suppression of IP by up-regulating HLA class 1, IRF1, ICAM1 and CADM1
expression of which CADM1 was confirmed to be a direct target of miR-486-
5p. Transcriptome profiling of primary human epidermal keratinocytes
overexpressing miR-486-5p revealed damping the signalling pathways
associated with inflammatory chemokines, cytokines and interleukins.
Taken together, these data suggest that miR-486-5p plays a protective role
in the pathogenesis of AA by maintaining anagen phase and preventing the
IP collapse. / National Alopecia Areata Foundation
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/19059 |
| Date | January 2020 |
| Creators | Broadley, David P. |
| Contributors | Botchkareva, Natalia V., Mardaryev, Andrei N. |
| Publisher | University of Bradford, Centre for Skin Sciences, Faculty of Life Sciences |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Thesis, doctoral, PhD |
| Rights | <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>. |
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