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miR-203 promotes HaCaT cell overproliferation through targeting LXR-α and PPAR-γ
- Publication Year :
- 2020
- Publisher :
- Taylor & Francis, 2020.
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Abstract
- Psoriasis is an immune-mediated chronic inflammatory skin disease. Keratinocyte hyperproliferation has been regarded as a significant event in psoriasis pathogenesis. Considering the vital role of miRNA-mediated mRNA repression in psoriasis pathogenesis, in the present study, we attempted to investigate the mechanism of keratinocyte overproliferation from the point of miRNA-mRNA regulation. Both online microarray expression profiles and experimental results indicated that the expression of LXR-α and PPAR-γ was downregulated in psoriasis lesion skin. LXR-α or PPAR-γ overexpression alone was sufficient to inhibit keratinocyte proliferation, decrease KRT5 and KRT14 protein levels and increase KRT1 and KRT10 protein levels. miR-203 negatively regulated LXR-α and PPAR-γ expression through direct targeting. miR-203 inhibition exerted the opposite effects to LXR-α or PPAR-γ overexpression on HaCaT cells. More importantly, LXR-α or PPAR-γ overexpression could markedly remarkably attenuate the effects of miR-203 overexpression in keratinocytes, indicating that miR-203 promotes keratinocyte proliferation by targeting LXR-α and PPAR-γ. In conclusion, the miR-203-LXR-α/PPAR-γ axis modulates the proliferation of keratinocytes and might be a novel target for psoriasis treatment, which needs further in vivo investigation.
- Subjects :
- lipids (amino acids, peptides, and proteins)
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....63c9e3d0ff3cdf63cb928ab44fb17b06
- Full Text :
- https://doi.org/10.6084/m9.figshare.12851531