New Insights in Photoaging Process Revealed by In Vitro Reconstructed Skin Models

  • Claire Marionnet
  • Christine Duval
  • Françoise Bernerd
Living reference work entry


Photoaging, clinically characterized by wrinkles, sagging, and age spots, mostly results from chronic impacts of solar ultraviolet (UV) rays affecting the whole skin, from surface to deep dermis. Three-dimensional (3-D) organotypic skin models represent useful in vitro tools to better understand the early UV-induced biological events. Such systems not only allow to reproduce in vitro well-known biomarkers for sunburn reaction but also to identify new key biological alterations induced by UVA exposure and involved in dermal photoaging process. Based upon new scientific proofs of the harmful role of chronic suberythemal UV exposures, the effects of exposures to nonextreme daily UV spectrum, mimicking more realistic everyday life conditions, have revealed a true biological impact upon skin with a strong oxidative stress and a major contribution of UVA rays. More recent data have demonstrated the damaging effects of long UVA wavelengths (UVA1), although less energetic than UVB or UVA2. UVA1 exposure could actually induce the production of reactive oxygen species (ROS) and DNA lesions but also impair several major biological functions and pathways in both epidermis and dermis. These data are in line with recent in vivo data, altogether strongly supporting the need for an adequate UVA1 photoprotection. Finally, the development of a full-thickness pigmented skin model allows to prove the role of dermal fibroblasts on the pigmentary function, showing that the photoaging of dermal fibroblasts can stimulate skin pigmentation. A link between photoaging-induced dermal alterations and pigmentary changes could then be established thanks to an appropriate in vitro skin model.


Dermal Fibroblast Skin Pigmentation Skin Model Dermal Equivalent UVA1 Exposure 
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  1. 1.
    Flament F, Bazin R, Laquieze S, Rubert V, Simonpietri E, Piot B. Effect of the sun on visible clinical signs of aging in Caucasian skin. Clin Cosmet Invest Dermatol. 2013;6:221–32.CrossRefGoogle Scholar
  2. 2.
    Gunn DA, Rexbye H, Griffiths CE, Murray PG, Fereday A, Catt SD, Tomlin CC, Strongitharm BH, Perrett DI, Catt M, Mayes AE, Messenger AG, Green MR, van der Ouderaa F, Vaupel JW, Christensen K. Why some women look young for their age. PLoS One. 2009;4:e8021.PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Gordon JR, Brieva JC. Images in clinical medicine. Unilateral dermatoheliosis. N Engl J Med. 2012;366:e25.CrossRefPubMedGoogle Scholar
  4. 4.
    Ortonne JP, Bissett DL. Latest insights into skin hyperpigmentation. J Invest Dermatol Symp Proc. 2008;13:10–4.CrossRefGoogle Scholar
  5. 5.
    Tagami H. Functional characteristics of the stratum corneum in photoaged skin in comparison with those found in intrinsic aging. Arch Dermatol Res. 2008;300 Suppl 1:S1–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Lavker RM. Cutaneous aging: chronologic versus photoaging. In: Gilchrest BA, editor. Photodamage. Cambridge, MA: Blackwell; 1995. p. 123–35.Google Scholar
  7. 7.
    Talwar HS, Griffiths CE, Fisher GJ, Hamilton TA, Voorhees JJ. Reduced type I and type III procollagens in photodamaged adult human skin. J Invest Dermatol. 1995;105:285–90.CrossRefPubMedGoogle Scholar
  8. 8.
    Jeanmaire C, Danoux L, Pauly G. Glycation during human dermal intrinsic and actinic ageing: an in vivo and in vitro model study. Br J Dermatol. 2001;145:10–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Bernstein EF, Fisher LW, Li K, LeBaron RG, Tan EM, Uitto J. Differential expression of the versican and decorin genes in photoaged and sun-protected skin. Comparison by immunohistochemical and northern analyses. Lab Invest. 1995;72:662–9.PubMedGoogle Scholar
  10. 10.
    Chen VL, Fleischmajer R, Schwartz E, Palaia M, Timpl R. Immunochemistry of elastotic material in sun-damaged skin. J Invest Dermatol. 1986;87:334–7.CrossRefPubMedGoogle Scholar
  11. 11.
    Chung JH, Seo JY, Choi HR, Lee MK, Youn CS, Rhie G, Cho KH, Kim KH, Park KC, Eun HC. Modulation of skin collagen metabolism in aged and photoaged human skin in vivo. J Invest Dermatol. 2001;117:1218–24.CrossRefPubMedGoogle Scholar
  12. 12.
    Fisher GJ, Datta SC, Talwar HS, Wang ZQ, Varani J, Kang S, Voorhees JJ. Molecular basis of sun-induced premature skin ageing and retinoid antagonism. Nature. 1996;379:335–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Berneburg M, Plettenberg H, Krutmann J. Photoaging of human skin. Photodermatol Photoimmunol Photomed. 2000;16:239–44.CrossRefPubMedGoogle Scholar
  14. 14.
    Fisher GJ, Voorhees JJ. Molecular mechanisms of photoaging and its prevention by retinoic acid: ultraviolet irradiation induces MAP kinase signal transduction cascades that induce Ap-1-regulated matrix metalloproteinases that degrade human skin in vivo. J Invest Dermatol Symp Proc. 1998;3:61–8.Google Scholar
  15. 15.
    Ma W, Wlaschek M, Tantcheva-Poor I, Schneider LA, Naderi L, Razi-Wolf Z, Schuller J, Scharffetter-Kochanek K. Chronological ageing and photoageing of the fibroblasts and the dermal connective tissue. Clin Exp Dermatol. 2001;26:592–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Seite S, Zucchi H, Septier D, Igondjo-Tchen S, Senni K, Godeau G. Elastin changes during chronological and photo-ageing: the important role of lysozyme. J Eur Acad Dermatol Venereol. 2006;20:980–7.PubMedGoogle Scholar
  17. 17.
    Hase T, Shinta K, Murase T, Tokimitsu I, Hattori M, Takimoto R, Tsuboi R, Ogawa H. Histological increase in inflammatory infiltrate in sun-exposed skin of female subjects: the possible involvement of matrix metalloproteinase-1 produced by inflammatory infiltrate on collagen degradation. Br J Dermatol. 2000;142:267–73.CrossRefPubMedGoogle Scholar
  18. 18.
    Li Y, Xia W, Liu Y, Remmer HA, Voorhees J, Fisher GJ. Solar ultraviolet irradiation induces decorin degradation in human skin likely via neutrophil elastase. PLoS One. 2013;8:e72563.PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Cario-Andre M, Lepreux S, Pain C, Nizard C, Noblesse E, Taieb A. Perilesional vs. lesional skin changes in senile lentigo. J Cutan Pathol. 2004;31:441–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Andersen WK, Labadie RR, Bhawan J. Histopathology of solar lentigines of the face: a quantitative study. J Am Acad Dermatol. 1997;36:444–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Unver N, Freyschmidt-Paul P, Horster S, Wenck H, Stab F, Blatt T, Elsasser HP. Alterations in the epidermal-dermal melanin axis and factor XIIIa melanophages in senile lentigo and ageing skin. Br J Dermatol. 2006;155:119–28.CrossRefPubMedGoogle Scholar
  22. 22.
    Chen N, Hu Y, Li WH, Eisinger M, Seiberg M, Lin CB. The role of keratinocyte growth factor in melanogenesis: a possible mechanism for the initiation of solar lentigines. Exp Dermatol. 2010;19:865–72.CrossRefPubMedGoogle Scholar
  23. 23.
    Iriyama S, Ono T, Aoki H, Amano S. Hyperpigmentation in human solar lentigo is promoted by heparanase-induced loss of heparan sulfate chains at the dermal-epidermal junction. J Dermatol Sci. 2011;64:223–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Fagot D, Asselineau D, Bernerd F. Direct role of human dermal fibroblasts and indirect participation of epidermal keratinocytes in MMP-1 production after UV-B irradiation. Arch Dermatol Res. 2002;293:576–83.CrossRefPubMedGoogle Scholar
  25. 25.
    Fagot D, Asselineau D, Bernerd F. Matrix metalloproteinase-1 production observed after solar-simulated radiation exposure is assumed by dermal fibroblasts but involves a paracrine activation through epidermal keratinocytes. Photochem Photobiol. 2004;79:499–505.CrossRefPubMedGoogle Scholar
  26. 26.
    Wlaschek M, Tantcheva-Poor I, Naderi L, Ma W, Schneider LA, Razi-Wolf Z, Schuller J, Scharffetter-Kochanek K. Solar UV irradiation and dermal photoaging. J Photochem Photobiol B. 2001;63:41–51.CrossRefPubMedGoogle Scholar
  27. 27.
    Krutmann J. Ultraviolet A radiation-induced biological effects in human skin: relevance for photoaging and photodermatosis. J Dermatol Sci. 2000;23 Suppl 1:S22–6.CrossRefPubMedGoogle Scholar
  28. 28.
    Commission Internationale de l’Éclairage (CIE). Solar spectral irradiance. Technical report, CIE 085–1989,, Vienna; 1989.Google Scholar
  29. 29.
    Lubin D, Jensen EH. Effects of clouds and stratospheric ozone depletion on ultraviolet radiation trends. Nature. 1995;377:710–3.CrossRefGoogle Scholar
  30. 30.
    Sabziparvar AA, Shine KP, Forster PMD. A model-derived global climatology of UV irradiation at the Earth’s surface. Photochem Photobiol. 1999;69:193–202.Google Scholar
  31. 31.
    Tewari A, Grage MM, Harrison GI, Sarkany R, Young AR. UVA1 is skin deep: molecular and clinical implications. Photochem Photobiol Sci. 2013;12:95–103.CrossRefPubMedGoogle Scholar
  32. 32.
    Seite S, Fourtanier A, Moyal D, Young AR. Photodamage to human skin by suberythemal exposure to solar ultraviolet radiation can be attenuated by sunscreens: a review. Br J Dermatol. 2010;163:903–14.CrossRefPubMedGoogle Scholar
  33. 33.
    Mahe E, Correa MP, Godin-Beekmann S, Haeffelin M, Jegou F, Saiag P, Beauchet A. Evaluation of tourists’ UV exposure in Paris. J Eur Acad Dermatol Venereol. 2013;27:e294–304.CrossRefPubMedGoogle Scholar
  34. 34.
    Eungdamrong NJ, Higgins C, Guo Z, Lee WH, Gillette B, Sia S, Christiano AM. Challenges and promises in modeling dermatologic disorders with bioengineered skin. Exp Biol Med (Maywood). 2014;239:1215–24.CrossRefGoogle Scholar
  35. 35.
    Bernerd F, Asselineau D, Vioux C, Chevallier-Lagente O, Bouadjar B, Sarasin A, Magnaldo T. Clues to epidermal cancer proneness revealed by reconstruction of DNA repair-deficient xeroderma pigmentosum skin in vitro. Proc Natl Acad Sci U S A. 2001;98:7817–22.PubMedCentralCrossRefPubMedGoogle Scholar
  36. 36.
    Haake AR, Polakowska RR. UV-induced apoptosis in skin equivalents: inhibition by phorbol ester and Bcl-2 overexpression. Cell Death Differ. 1995;2:183–93.PubMedGoogle Scholar
  37. 37.
    Bernerd F, Asselineau D. Successive alteration and recovery of epidermal differentiation and morphogenesis after specific UVB-damages in skin reconstructed in vitro. Dev Biol. 1997;183:123–38.CrossRefPubMedGoogle Scholar
  38. 38.
    Vioux-Chagnoleau C, Lejeune F, Sok J, Pierrard C, Marionnet C, Bernerd F. Reconstructed human skin: from photodamage to sunscreen photoprotection and anti-aging molecules. J Dermatol Sci. 2006;2(Suppl):S1–12.Google Scholar
  39. 39.
    Fernandez TL, Van Lonkhuyzen DR, Dawson RA, Kimlin MG, Upton Z. Characterization of a human skin equivalent model to study the effects of ultraviolet B radiation on keratinocytes. Tissue Eng Part C Methods. 2014;20:588–98.PubMedCentralCrossRefPubMedGoogle Scholar
  40. 40.
    Lavker RM, Veres DA, Irwin CJ, Kaidbey KH. Quantitative assessment of cumulative damage from repetitive exposures to suberythemogenic doses of UVA in human skin. Photochem Photobiol. 1995;62:348–52.CrossRefPubMedGoogle Scholar
  41. 41.
    Berneburg M, Krutmann J. Mitochondrial DNA deletions in human skin reflect photo- rather than chronologic aging. J Invest Dermatol. 1998;111:709–10.CrossRefPubMedGoogle Scholar
  42. 42.
    Bernerd F, Asselineau D. UVA exposure of human skin reconstructed in vitro induces apoptosis of dermal fibroblasts: subsequent connective tissue repair and implications in photoaging. Cell Death Differ. 1998;5:792–802.CrossRefPubMedGoogle Scholar
  43. 43.
    Marionnet C, Grether-Beck S, Seite S, Marini A, Jaenicke T, Lejeune F, Bastien P, Rougier A, Bernerd F, Krutmann J. A broad-spectrum sunscreen prevents UVA radiation-induced gene expression in reconstructed skin in vitro and in human skin in vivo. Exp Dermatol. 2011;20:477–82.CrossRefPubMedGoogle Scholar
  44. 44.
    Meloni M, Farina A, de Servi B. Molecular modifications of dermal and epidermal biomarkers following UVA exposures on reconstructed full-thickness human skin. Photochem Photobiol Sci. 2010;9:439–47.CrossRefPubMedGoogle Scholar
  45. 45.
    Dekker P, Parish WE, Green MR. Protection by food-derived antioxidants from UV-A1-induced photodamage, measured using living skin equivalents. Photochem Photobiol. 2005;81:837–42.CrossRefPubMedGoogle Scholar
  46. 46.
    Tewari A, Sarkany RP, Young AR. UVA1 induces cyclobutane pyrimidine dimers but not 6–4 photoproducts in human skin in vivo. J Invest Dermatol. 2012;132:394–400.CrossRefPubMedGoogle Scholar
  47. 47.
    Huang XX, Bernerd F, Halliday GM. Ultraviolet A within sunlight induces mutations in the epidermal basal layer of engineered human skin. Am J Pathol. 2009;174:1534–43.PubMedCentralCrossRefPubMedGoogle Scholar
  48. 48.
    Jonason AS, Kunala S, Price GJ, Restifo RJ, Spinelli HM, Persing JA, Leffell DJ, Tarone RE, Brash DE. Frequent clones of p53-mutated keratinocytes in normal human skin. Proc Natl Acad Sci U S A. 1996;93:14025–9.PubMedCentralCrossRefPubMedGoogle Scholar
  49. 49.
    Fisher GJ, Wang ZQ, Datta SC, Varani J, Kang S, Voorhees JJ. Pathophysiology of premature skin aging induced by ultraviolet light. N Engl J Med. 1997;337:1419–28.CrossRefPubMedGoogle Scholar
  50. 50.
    Deutsches Institut für Normung e.V.(DIN). Experimentelle Bewertung des Erythemschutzes von externen Sonnenschutzmitteln für die menschliche Haut (Experimental evaluation of the protection from erythema by external sunscreen products for the human skin). Berlin; 1999.Google Scholar
  51. 51.
    Commission Internationale de l’Eclairage (CIE). Spectral weighting of solar ultraviolet radiation. 2003. CIE 151, Vienna. Ref Type: Report.
  52. 52.
    Bissonauth V, Drouin R, Mitchell DL, Rhainds M, Claveau J, Rouabhia M. The efficacy of a broad-spectrum sunscreen to protect engineered human skin from tissue and DNA damage induced by solar ultraviolet exposure. Clin Cancer Res. 2000;6:4128–35.PubMedGoogle Scholar
  53. 53.
    Bernerd F, Vioux C, Lejeune F, Asselineau D. The sun protection factor (SPF) inadequately defines broad spectrum photoprotection: demonstration using skin reconstructed in vitro exposed to UVA, UVBor UV-solar simulated radiation. Eur J Dermatol. 2003;13:242–9.PubMedGoogle Scholar
  54. 54.
    Christiaens FJ, Chardon A, Fourtanier A, Frederick JE. Standard ultraviolet daylight for nonextreme exposure conditions. Photochem Photobiol. 2005;81:874–8.CrossRefPubMedGoogle Scholar
  55. 55.
    Marionnet C, Tricaud C, Bernerd F. Exposure to non-extreme solar UV daylight: spectral characterization, effects on skin and photoprotection. Int J Mol Sci. 2014;16:68–90.Google Scholar
  56. 56.
    Seite S, Medaisko C, Christiaens F, Bredoux C, Compan D, Zucchi H, Lombard D, Fourtanier A. Biological effects of simulated ultraviolet daylight: a new approach to investigate daily photoprotection. Photodermatol Photoimmunol Photomed. 2006;22:67–77.CrossRefPubMedGoogle Scholar
  57. 57.
    Marionnet C, Pierrard C, Lejeune F, Sok J, Thomas M, Bernerd F. Different oxidative stress response in keratinocytes and fibroblasts of reconstructed skin exposed to non extreme daily-ultraviolet radiation. PLoS One. 2010;5:e12059.PubMedCentralCrossRefPubMedGoogle Scholar
  58. 58.
    Leccia MT, Richard MJ, Joanny-Crisci F, Beani JC. UV-A1 cytotoxicity and antioxidant defence in keratinocytes and fibroblasts. Eur J Dermatol. 1998;8:478–82.PubMedGoogle Scholar
  59. 59.
    Matsuda M, Hoshino T, Yamakawa N, Tahara K, Adachi H, Sobue G, Maji D, Ihn H, Mizushima T. Suppression of UV-induced wrinkle formation by induction of HSP70 expression in mice. J Invest Dermatol. 2013;133:919–28.CrossRefPubMedGoogle Scholar
  60. 60.
    Marionnet C, Pierrard C, Lejeune F, Bernerd F. Modulations of gene expression induced by daily ultraviolet light can be prevented by a broad spectrum sunscreen. J Photochem Photobiol B. 2012;116:37–47.CrossRefPubMedGoogle Scholar
  61. 61.
    Norval M, Halliday GM. The consequences of UV-induced immunosuppression for human health. Photochem Photobiol. 2011;87:965–77.CrossRefPubMedGoogle Scholar
  62. 62.
    Marionnet C, Lejeune F, Pierrard C, Vioux-Chagnoleau C, Bernerd F. Biological contribution of UVA wavelengths in non extreme daily UV exposure. J Dermatol Sci. 2012;66:238–40.CrossRefPubMedGoogle Scholar
  63. 63.
    de Laat A, van der Leun JC, de Gruijl FR. Carcinogenesis induced by UVA (365-nm) radiation: the dose-time dependence of tumor formation in hairless mice. Carcinogenesis. 1997;18(5):1013–20.CrossRefPubMedGoogle Scholar
  64. 64.
    Damian DL, Matthews YJ, Phan TA, Halliday GM. An action spectrum for ultraviolet radiation-induced immunosuppression in humans. Br J Dermatol. 2011;164:657–9.PubMedGoogle Scholar
  65. 65.
    Wang F, Smith NR, Tran BA, Kang S, Voorhees JJ, Fisher GJ. Dermal damage promoted by repeated low-level UV-A1 exposure despite tanning response in human skin. JAMA Dermatol. 2014;150:401–6.PubMedCentralCrossRefPubMedGoogle Scholar
  66. 66.
    Marionnet C, Pierrard C, Golebiewski C, Bernerd F. Diversity of biological effects induced by longwave UVA rays (UVA1) in reconstructed skin. PLoS One. 2014;9:e105263.PubMedCentralCrossRefPubMedGoogle Scholar
  67. 67.
    Tewari A, Sarkany RP, Young AR. UVA1 induces cyclobutane pyrimidine dimers but not 6-4 photoproducts in human skin in vivo. J Invest Dermatol. 2012; 132:394–400.Google Scholar
  68. 68.
    York NR, Jacobe HT. UVA1 phototherapy: a review of mechanism and therapeutic application. Int J Dermatol. 2010;49:623–30.CrossRefPubMedGoogle Scholar
  69. 69.
    Takaoka A, Hayakawa S, Yanai H, Stoiber D, Negishi H, Kikuchi H, Sasaki S, Imai K, Shibue T, Honda K, Taniguchi T. Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence. Nature. 2003;424:516–23.CrossRefPubMedGoogle Scholar
  70. 70.
    Kim EJ, Jin XJ, Kim YK, Oh IK, Kim JE, Park CH, Chung JH. UV decreases the synthesis of free fatty acids and triglycerides in the epidermis of human skin in vivo, contributing to development of skin photoaging. J Dermatol Sci. 2010;57:19–26.CrossRefPubMedGoogle Scholar
  71. 71.
    Randhawa M, Southall M, Samaras ST. Metabolomic analysis of sun exposed skin. Mol Biosyst. 2013;9:2045–50.CrossRefPubMedGoogle Scholar
  72. 72.
    Duval C, Regnier M, Schmidt R. Distinct melanogenic response of human melanocytes in mono-culture, in co-culture with keratinocytes and in reconstructed epidermis, to UV exposure. Pigment Cell Res. 2001;14:348–55.CrossRefPubMedGoogle Scholar
  73. 73.
    Imokawa G. Autocrine and paracrine regulation of melanocytes in human skin and in pigmentary disorders. Pigment Cell Res. 2004;17:96–110.CrossRefPubMedGoogle Scholar
  74. 74.
    Regnier M, Duval C, Galey JB, Philippe M, Lagrange A, Tuloup R, Schmidt R. Keratinocyte-melanocyte co-cultures and pigmented reconstructed human epidermis: models to study modulation of melanogenesis. Cell Mol Biol. 1999; 45:969–80.Google Scholar
  75. 75.
    Duval C, Smit NP, Kolb AM, Regnier M, Pavel S, Schmidt R. Keratinocytes control the pheo/eumelanin ratio in cultured normal human melanocytes. Pigment Cell Res. 2002;15:440–6.CrossRefPubMedGoogle Scholar
  76. 76.
    Duval C, Schmidt R, Regnier M, Facy V, Asselineau D, Bernerd F. The use of reconstructed human skin to evaluate UV-induced modifications and sunscreen efficacy. Exp Dermatol. 2003;12(Suppl):64–70.Google Scholar
  77. 77.
    Gibbs S, Murli S, De BG, Mulder A, Mommaas AM, Ponec M. Melanosome capping of keratinocytes in pigmented reconstructed epidermis-effect of ultraviolet radiation and 3-isobutyl-1-methyl-xanthine on melanogenesis. Pigment Cell Res. 2000;13:458–66.CrossRefPubMedGoogle Scholar
  78. 78.
    Bessou S, Surleve-Bazeille JE, Sorbier E, Taieb A. Ex vivo reconstruction of the epidermis with melanocytes and the influence of UVB. Pigment Cell Res. 1995; 8:241–9.CrossRefPubMedGoogle Scholar
  79. 79.
    Buffey JA, Messenger AG, Taylor M, Ashcroft AT, Westgate GE, MacNeil S. Extracellular matrix derived from hair and skin fibroblasts stimulates human skin melanocyte tyrosinase activity. Br J Dermatol. 1994;131:836–42.CrossRefPubMedGoogle Scholar
  80. 80.
    Hedley SJ, Wagner M, Bielby S, Smith-Thomas L, Gawkrodger DJ, Mac Neil S. The influence of extracellular matrix proteins on cutaneous and uveal melanocytes. Pigment Cell Res. 1997;10:54–9.CrossRefPubMedGoogle Scholar
  81. 81.
    Scott G, Cassidy L, Busacco A. Fibronectin suppresses apoptosis in normal human melanocytes through an integrin-dependent mechanism. J Invest Dermatol. 1997;108:147–53.CrossRefPubMedGoogle Scholar
  82. 82.
    Yamaguchi Y, Itami S, Watabe H, Yasumoto K, Abdel-Malek ZA, Kubo T, Rouzaud F, Tanemura A, Yoshikawa K, Hearing VJ. Mesenchymal-epithelial interactions in the skin: increased expression of dickkopf1 by palmoplantar fibroblasts inhibits melanocyte growth and differentiation. J Cell Biol. 2004;165:275–85.PubMedCentralCrossRefPubMedGoogle Scholar
  83. 83.
    Choi W, Wolber R, Gerwat W, Mann T, Batzer J, Smuda C, Liu H, Kolbe L, Hearing VJ. The fibroblast-derived paracrine factor neuregulin-1 has a novel role in regulating the constitutive color and melanocyte function in human skin. J Cell Sci. 2010;123:3102–11.PubMedCentralCrossRefPubMedGoogle Scholar
  84. 84.
    Yamamoto T, Sawada Y, Katayama I, Nishioka K. Local expression and systemic release of stem cell factor in systemic sclerosis with diffuse hyperpigmentation. Br J Dermatol. 2001;144:199–200.CrossRefPubMedGoogle Scholar
  85. 85.
    Shishido E, Kadono S, Manaka I, Kawashima M, Imokawa G. The mechanism of epidermal hyperpigmentation in dermatofibroma is associated with stem cell factor and hepatocyte growth factor expression. J Invest Dermatol. 2001;117:627–33.CrossRefPubMedGoogle Scholar
  86. 86.
    Okazaki M, Yoshimura K, Suzuki Y, Uchida G, Kitano Y, Harii K, Imokawa G. The mechanism of epidermal hyperpigmentation in cafe-au-lait macules of neurofibromatosis type 1 (von Recklinghausen’s disease) may be associated with dermal fibroblast-derived stem cell factor and hepatocyte growth factor. Br J Dermatol. 2003;148:689–97.CrossRefPubMedGoogle Scholar
  87. 87.
    Cardinali G, Kovacs D, Giglio MD, Cota C, Aspite N, Mantea A, Girolomoni G, Picardo M. A kindred with familial progressive hyperpigmentation-like disorder: implication of fibroblast-derived growth factors in pigmentation. Eur J Dermatol. 2009;19:469–73.PubMedGoogle Scholar
  88. 88.
    Chung H, Jung H, Lee JH, Oh HY, Kim OB, Han IO, Oh ES. Keratinocyte-derived Laminin-332 protein promotes melanin synthesis via regulation of tyrosine uptake. J Biol Chem. 2014;289:21751–9.PubMedCentralCrossRefPubMedGoogle Scholar
  89. 89.
    Imokawa G, Yada Y, Morisaki N, Kimura M. Biological characterization of human fibroblast-derived mitogenic factors for human melanocytes. Biochem J. 1998;330:1235–9.Google Scholar
  90. 90.
    Mildner M, Mlitz V, Gruber F, Wojta J, Tschachler E. Hepatocyte growth factor establishes autocrine and paracrine feedback loops for the protection of skin cells after UV irradiation. J Invest Dermatol. 2007;127:2637–44.CrossRefPubMedGoogle Scholar
  91. 91.
    Kovacs D, Cardinali G, Aspite N, Cota C, Luzi F, Bellei B, Briganti S, Amantea A, Torrisi MR, Picardo M. Role of fibroblast-derived growth factors in regulating hyperpigmentation of solar lentigo. Br J Dermatol. 2010;163:1020–7.CrossRefPubMedGoogle Scholar
  92. 92.
    Cario-Andre M, Pain C, Gauthier Y, Casoli V, Taieb A. In vivo and in vitro evidence of dermal fibroblasts influence on human epidermal pigmentation. Pigment Cell Res. 2006;19:434–42.CrossRefPubMedGoogle Scholar
  93. 93.
    Souto LR, Rehder J, Vassallo J, Cintra ML, Kraemer MH, Puzzi MB. Model for human skin reconstructed in vitro composed of associated dermis and epidermis. Sao Paulo Med J. 2006;124:71–6.CrossRefPubMedGoogle Scholar
  94. 94.
    Okazaki M, Suzuki Y, Yoshimura K, Harii K. Construction of pigmented skin equivalent and its application to the study of congenital disorders of pigmentation. Scand J Plast Reconstr Surg Hand Surg. 2005;39:339–43.CrossRefPubMedGoogle Scholar
  95. 95.
    Duval C, Chagnoleau C, Pouradier F, Sextius P, Condom E, Bernerd F. Human skin model containing melanocytes: essential role of keratinocyte growth factor for constitutive pigmentation-functional response to alpha-melanocyte stimulating hormone and forskolin. Tissue Eng Part C Methods. 2012;18:947–57.CrossRefPubMedGoogle Scholar
  96. 96.
    Shin J, Kim JH, Kim EK. Repeated exposure of human fibroblasts to UVR induces secretion of stem cell factor and senescence. J Eur Acad Dermatol Venereol. 2012;26:1577–80.PubMedGoogle Scholar
  97. 97.
    Hirobe T, Hasegawa K, Furuya R, Fujiwara R, Sato K. Effects of fibroblast-derived factors on the proliferation and differentiation of human melanocytes in culture. J Dermatol Sci. 2013;71:45–57.CrossRefPubMedGoogle Scholar
  98. 98.
    Salducci M, Andre N, Guere C, Martin M, Fitoussi R, Vie K, Cario-Andre M. Factors secreted by irradiated aged fibroblasts induce solar lentigo in pigmented reconstructed epidermis. Pigment Cell Melanoma Res. 2014;27:502–4.CrossRefPubMedGoogle Scholar
  99. 99.
    Duval C, Cohen C, Chagnoleau C, Flouret V, Bourreau E, Bernerd F. Key regulatory role of dermal fibroblasts in pigmentation as demonstrated using a reconstructed skin model: impact of photo-aging. PLoS One. 2014;9:e114182.PubMedCentralCrossRefPubMedGoogle Scholar
  100. 100.
    Pouyani T, Papp S, Schaffer L. Tissue-engineered fetal dermal matrices. In Vitro Cell Dev Biol Anim. 2012;48:493–506.CrossRefPubMedGoogle Scholar
  101. 101.
    Namazi MR, Fallahzadeh MK, Schwartz RA. Strategies for prevention of scars: what can we learn from fetal skin? Int J Dermatol. 2011;50:85–93.CrossRefPubMedGoogle Scholar
  102. 102.
    Varani J, Schuger L, Dame MK, Leonard C, Fligiel SE, Kang S, Fisher GJ, Voorhees JJ. Reduced fibroblast interaction with intact collagen as a mechanism for depressed collagen synthesis in photodamaged skin. J Invest Dermatol. 2004;122:1471–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Claire Marionnet
    • 1
  • Christine Duval
    • 1
  • Françoise Bernerd
    • 1
  1. 1.L’Oreal Research and InnovationAulnay sous BoisFrance

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