The thyroid hormone receptors regulate the expression of microRNAs with key roles in skin homeostasis.

Related Articles

The thyroid hormone receptors regulate the expression of microRNAs with key roles in skin homeostasis.

Thyroid. 2018 May 10;:

Authors: Ruiz-Llorente L, Contreras-Jurado C, Martínez-Fernández M, Paramio JM, Aranda A

Abstract
BACKGROUND: MicroRNAs (miRNAs) play a unique role in posttranscriptional regulation of gene expression and control different aspects of skin development, homeostasis and disease. Although it is generally accepted that thyroid hormones signaling is important in skin pathophysiology, the role of their nuclear receptors (TRs) in cutaneous miRNA expression has yet to be explored.
METHODS: We have used RNAseq to compare the skin miRnome of wild-type mice and genetically modified mice lacking both TRα1 and TRβ, the main thyroid hormone binding isoforms. Changes in miRNAs with a crucial role in skin physiopathology were confirmed by stem-loop quantitative PCR both in total skin and isolated keratinocytes and the levels of their target mRNAs were evaluated by real time PCR.
RESULTS: The skin of TRα1/TRβ knockout (TR KO) mice displays altered levels of more than 50 miRNAs. Among the down-regulated species are several miRNAs, including miR-21, miR-31, miR-34 and miR-203, with crucial roles in skin homeostasis. TRα1 appears to be the main isoform responsible for their regulation. Increased levels of gene transcripts previously shown to be bona fide targets of these miRNAs are also found in the skin and keratinocytes of TR-deficient mice. This suggests that multiple miRNAs that are downregulated in the absence of TRs cooperate to regulate gene expression in the skin.
CONCLUSIONS: As the miRNAs reduced in TRα1/TRβ knockout mice are known to play crucial roles in epidermal proliferation, hair cycling, wound healing, stem cell function and tumor development, all of them processes altered in the absence of TRs, our results suggest that their regulation could contribute to the skin defects found in these mice and to the skin disorders associated with altered thyroid status in humans.

PMID: 29742977 [PubMed - as supplied by publisher]

https://ift.tt/2IvpX8R