Cited by 114melanin and skin pigmentationDermatologic Treatments and ResearchMelanoma and MAPK Pathways

Key Regulatory Role of Dermal Fibroblasts in Pigmentation as Demonstrated Using a Reconstructed Skin Model: Impact of Photo-Aging

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Duval, Christine, Cohen, Catherine, Chagnoleau, Corinne, Flouret, Virginie, Bourreau, Emilie, Bernerd, Françoise·2014·PLoS ONE

Abstract

To study cutaneous pigmentation in a physiological context, we have previously developed a functional pigmented reconstructed skin model composed of a melanocyte-containing epidermis grown on a dermal equivalent comprising living fibroblasts. The present studies, using the same model, aimed to demonstrate that dermal fibroblasts influence skin pigmentation up to the macroscopic level. The proof of principle was performed with pigmented skins differing only in the fibroblast component. First, the in vitro system was reconstructed with or without fibroblasts in order to test the global influence of the presence of this cell type. We then assessed the impact of the origin of the fibroblast strain on the degree of pigmentation using fetal versus adult fibroblasts. In both experiments, impressive variation in skin pigmentation at the macroscopic level was observed and confirmed by quantitative parameters related to skin color, melanin content and melanocyte numbers. These data confirmed the responsiveness of the model and demonstrated that dermal fibroblasts do indeed impact the degree of skin pigmentation. We then hypothesized that a physiological state associated with pigmentary alterations such as photo-aging could be linked to dermal fibroblasts modifications that accumulate over time. Pigmentation of skin reconstructed using young unexposed fibroblasts (n = 3) was compared to that of tissues containing natural photo-aged fibroblasts (n = 3) which express a senescent phenotype. A stimulation of pigmentation in the presence of the natural photo-aged fibroblasts was revealed by a significant increase in the skin color (decrease in Luminance) and an increase in both epidermal melanin content and melanogenic gene expression, thus confirming our hypothesis. Altogether, these data demonstrate that the level of pigmentation of the skin model is influenced by dermal fibroblasts and that natural photo-aged fibroblasts can contribute to the hyperpigmentation that is associated with photo-aging.

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  • Aging skin fibroblasts cause pigmentation and dark spots by promoting transcription of the melanin gene.

    “Further, aging skin fibroblasts cause pigmentation and dark spots by promoting the transcription of the melanin gene [28].”

    From Diet and Skin Aging—From the Perspective of Food Nutrition (2020) · cites this paper as [28]

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Research works printed but not linked: 4

  1. [43]Lavker R.M. (1995) Cutaneous aging: chronologic versus photoaging. in: Gilchrest B.A. (ed): Photodamage. Cambridge USA, Blackwell Science Inc, pp 123–135.
  2. [52]Hedley SJ, Layton C, Heaton M, Chakrabarty KH, Dawson RA, Gawkrodger DJ, et al (2002) Fibroblasts play a regulatory role in the control of pigmentation in reconstructed human skin from skin types I and II. Pigment Cell Res 15: 49– 56. 11837456
  3. [53]Imokawa G, Yada Y, Morisaki N, Kimura M (1998) Biological characterization of human fibroblast-derived mitogenic factors for human melanocytes. Biochem J 330 (Pt 3): 1235– 1239. PMC1219267 9494091
  4. [65]Kovacs D, Cardinali G, Aspite N, Cota C, Luzi F, et al (2010) Role of fibroblast-derived growth factors in regulating hyperpigmentation of solar lentigo. Br J Dermatol 163: 1020– 1027. 20662835

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Authors
Duval, C., Cohen, C., Chagnoleau, C., Flouret, V., Bourreau, E., & Bernerd, F.
Affiliations
L'Oréal (France) (FR)
Corresponding author
Duval, Christine
Venue
PLoS ONE
Published
2014-12-09
Volume
9
Issue
12
Pages
e114182
ISSN
1932-6203 (ISSN-L)
OpenAlex
W1972398615
Cited by
114
References
64
Citations by year
2026: 6 · 2025: 8 · 2024: 13 · 2023: 6 · 2022: 8 · 2021: 13 · 2020: 8 · 2019: 12 · 2018: 19 · 2017: 12 · 2016: 7 · 2015: 2
FWCI
3.49
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
  • Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Keywords
dermal fibroblasts, skin pigmentation, reconstructed skin model, photoaging, fibroblast senescence, melanin content, melanocyte proliferation, hyperpigmentation, epidermis
MeSH terms
Adult, Animals, Fibroblasts, Humans, Light, Melanocytes, Skin, Skin Pigmentation, Keratinocytes, 3T3 Cells, Cellular Senescence, Mice

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