Archives of Dermatological Research

, Volume 300, Issue 1, pp 47–52

Photoaging-associated changes in epidermal proliferative cell fractions in vivo

  • Oh Sang Kwon
  • Hyeon Gyeong Yoo
  • Ji Hyun Han
  • Se Rah Lee
  • Jin Ho Chung
  • Hee Chul Eun
Short Communication


The epidermis is a dynamic epithelium with constant renewal throughout life. Epidermal homeostasis depends on two types of proliferative cells, keratinocyte stem cells (KSCs), and transit amplifying (TA) cells. In the case of chronologic aging, levels of KSCs tend to decrease and change functionally. However, little is known about the effect of photoaging on epidermal proliferative subtype populations. The aim of this study was to validate involucrin/β1-integrin ratio as a molecular marker of epidermal photoaging, and to investigate the effects of photoaging caused by chronic UV exposure on the proliferative subtype populations. A total of 15 male volunteers (age range 20–24 and 77–85 years, Fitzpatrick skin phototype III–IV) provided sun-exposed and sun-protected skin samples for real-time RT-PCR, Western blot analysis and immunostaining. Fractional changes in proliferative subtype populations in photoaged and chronologically aged skins were analyzed by flow cytometry. The expression of β1-integrin was found to be significantly reduced in photoaged skin and ratios of the expressions of involucrin to β1-integrin were increased 2.6-fold only in elderly subjects. Interestingly, immunostaining of the sun-exposed skins of elderly subjects showed aberrant β1-integrin expression over the basal layer and greater numbers of Ki-67-positive cells than in sun-protected buttock skin. Flow cytometric analysis revealed that the proportion of KSCs to TA cells was reversed in sun-exposed and sun-protected skins of elderly subjects. Our results suggest that KSC numbers may be lower in photoaged skin than in chronologically aged skin and could be applied to hyperplastic pattern of photoaging. These findings suggest that the epidermis of photoaged skin is impaired in terms of its proliferative potential by attempting to repair chronic UV exposure and that photoaging may be associated with alteration in the two proliferative cell fractions.


Photoaging Ultraviolet Keratinocyte stem cells Involucrin β1-integrin 


  1. 1.
    Fisher GJ, Wang ZQ, Datta SC, Varani J, Kang S, Voorhees JJ (1997) Pathophysiology of premature skin aging induced by ultraviolet light. N Engl J Med 337:1419–1428PubMedCrossRefGoogle Scholar
  2. 2.
    Fisher GJ, Kang S, Varani J, Bata-Csorgo Z, Wan Y, Datta S, Voorhees JJ (2002) Mechanisms of photoaging and chronological skin aging. Arch Dermatol 138:1462–1470PubMedCrossRefGoogle Scholar
  3. 3.
    Bosset S, Bonnet-Duquennoy M, Barre P, Chalon A, Lazou K, Kurfurst R, Bonte F, Schnebert S, Disant F, Le Varlet B, Nicolas JF (2003) Decreased expression of keratinocyte beta1 integrins in chronically sun-exposed skin in vivo. Br J Dermatol 148:770–778PubMedCrossRefGoogle Scholar
  4. 4.
    Le Varlet B, Chaudagne C, Saunois A, Barre P, Sauvage C, Berthouloux B, Meybeck A, Dumas M, Bonte F (1998) Age-related functional and structural changes in human dermo-epidermal junction components. J Investig Dermatol Symp Proc 3:172–179PubMedGoogle Scholar
  5. 5.
    Webb A, Li A, Kaur P (2004) Location and phenotype of human adult keratinocyte stem cells of the skin. Differentiation 72:387–395PubMedCrossRefGoogle Scholar
  6. 6.
    Kaur P (2006) Interfollicular epidermal stem cells: identification, challenges, potential. J Invest Dermatol 126:1450–1458PubMedCrossRefGoogle Scholar
  7. 7.
    Roh C, Lyle S (2006) Cutaneous stem cells and wound healing. Pediatr Res 59:100R-103RPubMedCrossRefGoogle Scholar
  8. 8.
    Youn SW, Kim DS, Cho HJ, Jeon SE, Bae IH, Yoon HJ, Park KC (2004) Cellular senescence induced loss of stem cell proportion in the skin in vitro. J Dermatol Sci 35:113–123PubMedCrossRefGoogle Scholar
  9. 9.
    Chung JH, Lee SH, Youn CS, Park BJ, Kim KH, Park KC, Cho KH, Eun HC (2001) Cutaneous photodamage in Koreans: influence of sex, sun exposure, smoking, and skin color. Arch Dermatol 137:1043–1051PubMedGoogle Scholar
  10. 10.
    Griffiths CE, Russman AN, Majmudar G, Singer RS, Hamilton TA, Voorhees JJ (1993) Restoration of collagen formation in photodamaged human skin by tretinoin (retinoic acid). N Engl J Med 329:530–535PubMedCrossRefGoogle Scholar
  11. 11.
    Son ED, Lee JY, Lee S, Kim MS, Lee BG, Chang IS, Chung JH (2005) Topical application of 17beta-estradiol increases extracellular matrix protein synthesis by stimulating TGF-Beta signaling in aged human skin in vivo. J Invest Dermatol 124:1149–1161PubMedCrossRefGoogle Scholar
  12. 12.
    Willsteed EM, Bhogal BS, Das A, Bekir SS, Wojnarowska F, Black MM, Mckee PH (1991) An ultrastructural comparison of dermo-epidermal separation techniques. J Cutan Pathol 18:8–12PubMedCrossRefGoogle Scholar
  13. 13.
    Bata-Csorgo Z, Hammerberg C, Voorhees JJ, Cooper KD (1993) Flow cytometric identification of proliferative subpopulations within normal human epidermis and the localization of the primary hyperproliferative population in psoriasis. J Exp Med 178:1271–1281PubMedCrossRefGoogle Scholar
  14. 14.
    Chung JH, Seo JY, Choi HR, Lee MK, Youn CS, Rhie G, Cho KH, Kim KH, Park KC, Eun HC (2001) Modulation of skin collagen metabolism in aged and photoaged human skin in vivo. J Invest Dermatol 117:1218–1224PubMedCrossRefGoogle Scholar
  15. 15.
    Yaar M, Gilchrest BA (2001) Ageing and photoageing of keratinocytes and melanocytes. Clin Exp Dermatol 26:583–591PubMedCrossRefGoogle Scholar
  16. 16.
    Liu J, Finkel T (2006) Stem cell aging: what bleach can teach. Nat Med 12:383–384PubMedCrossRefGoogle Scholar
  17. 17.
    Bell DR, Van Zant G (2004) Stem cells, aging, and cancer: inevitabilities and outcomes. Oncogene 23:7290–7296PubMedCrossRefGoogle Scholar
  18. 18.
    Dunnwald M, Chinnathambi S, Alexandrunas D, Bickenbach JR (2003) Mouse epidermal stem cells proceed through the cell cycle. J Cell Physiol 195:194–201PubMedCrossRefGoogle Scholar
  19. 19.
    Watt FM (2002) Role of integrins in regulating epidermal adhesion, growth and differentiation. EMBO J 21:3919–3926PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Oh Sang Kwon
    • 1
  • Hyeon Gyeong Yoo
    • 1
  • Ji Hyun Han
    • 1
  • Se Rah Lee
    • 1
  • Jin Ho Chung
    • 1
  • Hee Chul Eun
    • 1
  1. 1.Department of Dermatology, Seoul National University College of Medicine, Laboratory of Cutaneous Aging and Hair Research, Clinical Research Institute, Seoul National University Hospital, Institute of Dermatological ScienceSeoul National UniversitySeoulSouth Korea

Personalised recommendations