Micro RNAs upregulated in Vitiligo skin play an important role in its aetiopathogenesis by altering TRP1 expression and keratinocyte-melanocytes cross-talk

Abstract

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.

The long noncoding RNA MALAT1 suppresses miR‐211 to confer protection from ultraviolet‐mediated DNA damage in vitiligo epidermis by upregulating sirtuin 1*

“…Although several differentially expressed miRNAs have been reported in the skin, 20–22 peripheral blood mononuclear cells 23 and sera of individuals with vitiligo, 24 our study forms the first comprehensive analysis of its epidermis‐specific microRNome. The high expression of miR‐203a, a known keratinocyte‐associated miRNA, 25 observed in both nonlesional and lesional samples, reiterates the epidermis‐specific nature of the miRNAs observed in our study.…”

SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the Wnt/β-catenin signaling

“…The formation and maturation of melanosomes and the ability to synthesize melanin are key to vitiligo repigmentation. 57 , 58 On the basis of its overexpression in vitiligo skin in vivo , we hypothesized that SFRP5 inhibits melanogenesis. Overexpression or silencing of SFRP5 expression was then achieved by recombinant or control adenoviruses, respectively, and the direct biological effects of SFRP5 on melanocytes were investigated.…”

Melanoma and Vitiligo: In Good Company

“…Interestingly, of the miRNAs reported by Huber et al on melanoma, miR-155 and miR-125b are up-regulated in vitiligo patients with respect to healthy individuals [102]. In addition, let-7e was found to be up-regulated in lesional compared with non-lesional epidermis [104], and miR-146a was up-regulated in the serum of vitiligo mice and vitiligo patients with respect to normal controls [111]. This last miR-146a is over-expressed also in other skin diseases such as in atopic dermatitis, and regulates differentiation of immune cells [112], whereas miR-155 and miR-125b have a role in melanogenesis [102].…”