Decreased expression of neuregulin1 in the lesional skin of vitiligo patients

Int J Dermatol. 2019 Feb;58(2):242-249. doi: 10.1111/ijd.14161. Epub 2018 Aug 3.

Abstract

Background: Paracrine cross-talk exists between the fibroblasts of dermis and epidermal cells through secretions of various growth factors. Melanocytes present at the basement layer of the epidermis and respond to various factors secreted by underlying dermal fibroblasts in the dermis to regulate the function of the skin.

Objective: Therefore the study was planned to check the expression of fibroblast-derived factor neuregulin1 (NRG1) in vitiligo skin and its effect on melanocytes.

Methods: For this study, relative gene expression at mRNA level of NRG1 in the vitiligo skin was analyzed by qRT-PCR, and protein analysis was done by immunohistochemistry. Effect of different concentrations of NRG1 was checked on the cultured melanocytes by melanin content assay, proliferation assay, and tyrosinase (TYR) assay. The effect of NRG1 was also checked on the level of melanocyte regulatory genes (MITF, c-KIT, TYR, DCT).

Results: Expression of NRG1 was significantly less in lesional dermis of vitiligo patients as compared to nonlesional and healthy control dermis both at mRNA as well as protein level. NRG1 treatment showed significant increase in proliferation, melanin content, TYR level, and gene expression level of melanocyte specific genes.

Conclusion: Treatment of NRG1 to the cultured melanocytes increases proliferation and pigmentation. Lower expression of NRG1 in the lesional dermis of vitiligo patients inhibits the melanocyte growth. Therefore this study hypothesized that low expression of NRG1 in lesional skin of vitiligo patients might have a possible role in the melanocyte loss and vitiligo pathogenesis.

MeSH terms

  • Adult
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Female
  • Gene Expression / drug effects
  • Humans
  • Male
  • Melanins / metabolism
  • Melanocytes / drug effects
  • Melanocytes / metabolism
  • Microphthalmia-Associated Transcription Factor / genetics
  • Monophenol Monooxygenase / genetics
  • Monophenol Monooxygenase / metabolism
  • Neuregulin-1 / genetics*
  • Neuregulin-1 / metabolism*
  • Neuregulin-1 / pharmacology
  • Proto-Oncogene Proteins c-kit / genetics
  • RNA, Messenger / metabolism*
  • Skin / metabolism*
  • Vitiligo / metabolism*
  • Young Adult

Substances

  • MITF protein, human
  • Melanins
  • Microphthalmia-Associated Transcription Factor
  • NRG1 protein, human
  • Neuregulin-1
  • RNA, Messenger
  • Monophenol Monooxygenase
  • KIT protein, human
  • Proto-Oncogene Proteins c-kit