Key Regulatory Role of Dermal Fibroblasts in Pigmentation as Demonstrated Using a Reconstructed Skin Model: Impact of Photo-Aging
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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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- 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
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-12-09
- Volume
- 9
- Issue
- 12
- Pages
- e114182
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4260844
- 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
- gold
- doi.org
- 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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