Micro RNAs upregulated in Vitiligo skin play an important role in its aetiopathogenesis by altering TRP1 expression and keratinocyte-melanocytes cross-talk.
Utpreksha VaishAvinash A KumarSwati VarshneyShreya GhoshShantanu SenguptaChandni SoodHemanta K KarPankaj SharmaVivek T NatarajanRajesh S GokhaleRajni RaniPublished in: Scientific reports (2019)
Translation of genes is regulated by many factors including microRNAs (miRNAs). miRNA profiling of lesional and non-lesional epidermal RNA from 18 vitiligo patients revealed significant upregulation of 29 miRNAs in the lesional epidermis, of which 6 miRNAs were transfected in normal human epidermal keratinocytes (NHEKs) to study their downstream effects using quantitative proteomics. Many proteins involved in oxidative stress, Vesicle trafficking, Cellular apoptosis, Mitochondrial proteins and Keratins were regulated after miRNA transfections in the keratinocytes. However, tyrosinase related protein-1 (TRP1/TYRP1), a melanogenesis protein, was consistently downregulated in NHEKs by all the six miRNAs tested, which was quite intriguing. TRP1 was also downregulated in lesional epidermis compared with non-lesional epidermis. Since melanocytes synthesize and transfer melanosomes to the surrounding keratinocytes, we hypothesized that downregulation of TRP1 in NHEKs may have a role in melanosome transfer, which was confirmed by our co-culture experiments. Downregulation of TRP1 in keratinocytes negatively affected the melanosome transfer from melanocytes to keratinocytes resulting in melanin accumulation which may be leading to melanin induced cytotoxicity in melanocytes. Regulation of key processes involved in aetiopathogenesis of vitiligo along with TRP1 suggests that miRNAs act in an integrated manner which may be detrimental for the loss of melanocytes in vitiligo.
Keyphrases
- wound healing
- oxidative stress
- poor prognosis
- cell proliferation
- diabetic rats
- end stage renal disease
- signaling pathway
- endothelial cells
- high resolution
- dna damage
- newly diagnosed
- ejection fraction
- chronic kidney disease
- cell death
- high glucose
- dna methylation
- endoplasmic reticulum stress
- patient reported outcomes
- ischemia reperfusion injury
- peritoneal dialysis
- long non coding rna
- amino acid
- induced pluripotent stem cells
- nucleic acid