Journal
PIGMENT CELL & MELANOMA RESEARCH
Volume 33, Issue 2, Pages 305-317Publisher
WILEY
DOI: 10.1111/pcmr.12826
Keywords
desmosomes; environment; keratinocytes; melanocytes; melanoma; skin; sunlight
Categories
Funding
- NIH/NIAMS [K01 AR075087, R01 AR041836]
- NIH/NCI [R01 CA122151]
- Liz and Eric Lefkofsky Family Foundation Innovation Research Award
- JL Mayberry endowment
- NIH/NCI Ruth L. Kirschstein Training Grant through Northwestern University's Robert H. Lurie Comprehensive Cancer Center [T32 CA070085, T32 CA080621-14]
- NIH/NCI Ruth L. Kirschstein National Research Service Award [1F32CA210498-01]
- Northwestern University Skin Disease Research Center [5P30AR057216]
- NCI CCSG [P30 CA060553]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [R13AR009431-53, R13AR07429-01]
- National Institute on Aging (NIA)
- National Institute of Environmental Sciences (NIEHS)
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The epidermis is the first line of defense against ultraviolet (UV) light from the sun. Keratinocytes and melanocytes respond to UV exposure by eliciting a tanning response dependent in part on paracrine signaling, but how keratinocyte:melanocyte communication is regulated during this response remains understudied. Here, we uncover a surprising new function for the keratinocyte-specific cell-cell adhesion molecule desmoglein 1 (Dsg1) in regulating keratinocyte:melanocyte paracrine signaling to promote the tanning response in the absence of UV exposure. Melanocytes within Dsg1-silenced human skin equivalents exhibited increased pigmentation and altered dendrite morphology, phenotypes which were confirmed in 2D culture using conditioned media from Dsg1-silenced keratinocytes. Dsg1-silenced keratinocytes increased melanocyte-stimulating hormone precursor (Pomc) and cytokine mRNA. Melanocytes cultured in media conditioned by Dsg1-silenced keratinocytes increased Mitf and Tyrp1 mRNA, TYRP1 protein, and melanin production and secretion. Melanocytes in Dsg1-silenced skin equivalents mislocalized suprabasally, reminiscent of early melanoma pagetoid behavior. Together with our previous report that UV reduces Dsg1 expression, these data support a role for Dsg1 in controlling keratinocyte:melanocyte paracrine communication and raise the possibility that a Dsg1-deficient niche contributes to pagetoid behavior, such as occurs in early melanoma development.
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