Cited by 61melanin and skin pigmentationMelanoma and MAPK PathwaysHair Growth and Disorders

Endothelin-1 is a transcriptional target of p53 in epidermal keratinocytes and regulates ultraviolet-induced melanocyte homeostasis

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Hyter, Stephen, Coleman, Daniel J., Ganguli‐Indra, Gitali, Merrill, Gary F., Ma, Steven, Yanagisawa, Masashi, Indra, Arup K.·2013·Pigment Cell & Melanoma Research

Abstract

Summary: Keratinocytes contribute to melanocyte activity by influencing their microenvironment, in part, through secretion of paracrine factors. Here, we discovered that p53 directly regulates Edn1 expression in epidermal keratinocytes and controls UV‐induced melanocyte homeostasis. Selective ablation of endothelin‐1 (EDN 1) in murine epidermis (EDN 1 ep−/−) does not alter melanocyte homeostasis in newborn skin but decreases dermal melanocytes in adult skin. Results showed that keratinocytic EDN 1 in a non‐cell autonomous manner controls melanocyte proliferation, migration, DNA damage, and apoptosis after ultraviolet B (UVB) irradiation. Expression of other keratinocyte‐derived paracrine factors did not compensate for the loss of EDN 1. Topical treatment with EDN 1 receptor (EDNRB) antagonist BQ 788 abrogated UV‐induced melanocyte activation and recapitulated the phenotype seen in EDN 1 ep−/− mice. Altogether, the present studies establish an essential role of EDN 1 in epidermal keratinocytes to mediate UV‐induced melanocyte homeostasis in vivo.

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  • Proposed mechanisms responsible for the role of neighbouring keratinocytes in mediating UVB-stimulated physiological responses of melanocytes in association with inhibition of oxidative stress likely involve paracrine effects of factors produced by epidermal keratinocytes.

    “Proposed mechanisms responsible for the role of neighbouring KC in mediating UVB-stimulated physiological responses of MC in association with inhibition of oxidative stress would likely involve the paracrine effects of factors produced by epidermal KC [7,9,10,13,35,36].”

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Authors
Hyter, S., Coleman, D. J., Ganguli‐Indra, G., Merrill, G. F., Ma, S., Yanagisawa, M., & Indra, A. K.
Affiliations
  • Oregon State University (US)
  • National Institute of Allergy and Infectious Diseases (US)
  • The University of Texas Southwestern Medical Center (US)
Corresponding author
Indra, Arup K.
Venue
Pigment Cell & Melanoma Research
Publisher
Wiley
Published
2013-01-24
Volume
26
Issue
2
Pages
247-258
ISSN
  • 1755-1471 (ISSN-L)
  • 1755-148X
OpenAlex
W2050938455
Cited by
61
References
43
Citations by year
2026: 2 · 2025: 6 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 6 · 2020: 4 · 2019: 4 · 2018: 6 · 2017: 9 · 2016: 4 · 2015: 5 · 2014: 3 · 2013: 2
FWCI
2.71
Type
journal article
Language
en
Open access
Locations
  • Pigment Cell & Melanoma Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Yale University
  • National Cancer Institute (T32CA106195)
  • National Institute of Environmental Health Sciences (ES016629-01A1, ES-00-210, R01ES016629, P30ES000210, T32ES007060)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
  • Health Sciences › Medicine › Urology › Hair Growth and Disorders
Keywords
endothelin-1, p53, epidermal keratinocytes, melanocyte homeostasis, UVB irradiation, BQ-788, paracrine signaling, melanocyte proliferation, melanocyte migration, melanocyte apoptosis, DNA damage, non-cell-autonomous regulation
MeSH terms
Epidermal Cells, Aging, Animals, DNA Damage, DNA Repair, Gene Expression Regulation, Homeostasis, Immunohistochemistry, Melanocytes, Organ Specificity, Phenotype, Protein Kinase C, Transcription, Genetic, Ultraviolet Rays, Keratinocytes, Tumor Suppressor Protein p53, Apoptosis, Gene Deletion, Endothelin-1, MAP Kinase Signaling System, Receptor, Endothelin B, Cell Proliferation, Mice

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