miRNAs are important post-transcriptional regulators of gene expression which
play vital roles in the arrays of physiological processes, including skin and hair
follicle (HF) development. In this study, the role for miR-214 in the skin and HF
development and their postnatal physiological regeneration was investigated.
miR-214 exhibits discrete expression patterns in the epidermis and HF in
developing and postnatal skin, and is highly expressed in the epithelial stem
cells and their lineage-committed progenies. The effects of miR-214 on HF
morphogenesis and cycle progression were evaluated by using doxycyclineinducible
miR-214 transgenic mice (K14-rtTA/TRE-miR-214). Keratinocyte
specific miR-214 overexpression during skin embryogenesis resulted in the
partial inhibition of HF induction and formation of the HF reduced in size
producing thinner hair. Overexpression of miR-214 in telogen skin caused
retardation of the anagen progression and HF growth. Inhibitory effects of miR-
214 on HF development and cycling were associated with supressed activity of
stem cells, reduced proliferation in the hair matrix, and altered differentiation.
miR-214 induced complex changes in gene expression programs in
keratinocytes, including inhibition of cyclins and cyclin-dependent kinases and
several essential components of Wnt, Edar, Shh and Bmp signalling pathways, whereas -catenin acts as a novel conserved miR-214 target. Indeed, the
inhibitory effects of miR-214 on HF development were rescued by
intracutaneous delivery of pharmacological Wnt activator.
Thus, this study demonstrated that by targeting -catenin and, therefore,
interfering with Wnt signalling activity miR-214 may act as one of the upstream
effectors of the signalling cascades which govern HF morphogenesis and
cycling.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/6481 |
| Date | January 2014 |
| Creators | Alam, Majid A. |
| Contributors | Botchkareva, Natalia V. |
| Publisher | University of Bradford, Medical Biosciences, School 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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