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 e...

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Autores principales:	Utpreksha Vaish, Avinash A. Kumar, Swati Varshney, Shreya Ghosh, Shantanu Sengupta, Chandni Sood, Hemanta K. Kar, Pankaj Sharma, Vivek T. Natarajan, Rajesh S. Gokhale, Rajni Rani
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Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0b173ece80484ae5b7782498aedb08fa
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spelling	oai:doaj.org-article:0b173ece80484ae5b7782498aedb08fa2021-12-02T15:08:32ZMicro RNAs upregulated in Vitiligo skin play an important role in its aetiopathogenesis by altering TRP1 expression and keratinocyte-melanocytes cross-talk10.1038/s41598-019-46529-62045-2322https://doaj.org/article/0b173ece80484ae5b7782498aedb08fa2019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-46529-6https://doaj.org/toc/2045-2322Abstract 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.Utpreksha VaishAvinash A. KumarSwati VarshneyShreya GhoshShantanu SenguptaChandni SoodHemanta K. KarPankaj SharmaVivek T. NatarajanRajesh S. GokhaleRajni RaniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-15 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Utpreksha Vaish Avinash A. Kumar Swati Varshney Shreya Ghosh Shantanu Sengupta Chandni Sood Hemanta K. Kar Pankaj Sharma Vivek T. Natarajan Rajesh S. Gokhale Rajni Rani Micro RNAs upregulated in Vitiligo skin play an important role in its aetiopathogenesis by altering TRP1 expression and keratinocyte-melanocytes cross-talk
description	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.
format	article
author	Utpreksha Vaish Avinash A. Kumar Swati Varshney Shreya Ghosh Shantanu Sengupta Chandni Sood Hemanta K. Kar Pankaj Sharma Vivek T. Natarajan Rajesh S. Gokhale Rajni Rani
author_facet	Utpreksha Vaish Avinash A. Kumar Swati Varshney Shreya Ghosh Shantanu Sengupta Chandni Sood Hemanta K. Kar Pankaj Sharma Vivek T. Natarajan Rajesh S. Gokhale Rajni Rani
author_sort	Utpreksha Vaish
title	Micro RNAs upregulated in Vitiligo skin play an important role in its aetiopathogenesis by altering TRP1 expression and keratinocyte-melanocytes cross-talk
title_short	Micro RNAs upregulated in Vitiligo skin play an important role in its aetiopathogenesis by altering TRP1 expression and keratinocyte-melanocytes cross-talk
title_full	Micro RNAs upregulated in Vitiligo skin play an important role in its aetiopathogenesis by altering TRP1 expression and keratinocyte-melanocytes cross-talk
title_fullStr	Micro RNAs upregulated in Vitiligo skin play an important role in its aetiopathogenesis by altering TRP1 expression and keratinocyte-melanocytes cross-talk
title_full_unstemmed	Micro RNAs upregulated in Vitiligo skin play an important role in its aetiopathogenesis by altering TRP1 expression and keratinocyte-melanocytes cross-talk
title_sort	micro rnas upregulated in vitiligo skin play an important role in its aetiopathogenesis by altering trp1 expression and keratinocyte-melanocytes cross-talk
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/0b173ece80484ae5b7782498aedb08fa
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Micro RNAs upregulated in Vitiligo skin play an important role in its aetiopathogenesis by altering TRP1 expression and keratinocyte-melanocytes cross-talk

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