Research Paper Volume 8, Issue 4 pp 751—768

Perlecan expression influences the keratin 15‐positive cell population fate in the epidermis of aging skin

Morgan Dos Santos 1, 2, , Anna Michopoulou 1, , Valérie André‐Frei 2, , Sophie Boulesteix 1, , Christine Guicher 1, , Guila Dayan 1, , John Whitelock 3, , Odile Damour 1, 4, , Patricia Rousselle 1, ,

  • 1 Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR 5305, CNRS, University Lyon 1, Lyon, France
  • 2 BASF BCS France SAS, 69366, Lyon, France
  • 3 Graduate School of Biomedical Engineering, University of New South Wales Sydney, Australia
  • 4 Cell and Tissue Bank, Hôpital Edouard Herriot, Lyon, France

received: January 13, 2016 ; accepted: February 23, 2016 ; published: March 17, 2016 ;
How to Cite


The epidermis is continuously renewed by stem cell proliferation and differentiation. Basal keratinocytes append the dermal‐epidermal junction, a cell surface‐associated, extracellular matrix that provides structural support and influences their behaviour. It consists of laminins, type IV collagen, nidogens, and perlecan, which are necessary for tissue organization and structural integrity. Perlecan is a heparan sulfate proteoglycan known to be involved in keratinocyte survival and differentiation. Aging affects the dermal epidermal junction resulting in decreased contact with keratinocytes, thus impacting epidermal renewal and homeostasis. We found that perlecan expression decreased during chronological skin aging. Our in vitro studies revealed reduced perlecan transcript levels in aged keratinocytes. The production of in vitro skin models revealed that aged keratinocytes formed a thin and poorly organized epidermis. Supplementing these models with purified perlecan reversed the phenomenon allowing restoration of a well‐differentiated multi‐layered epithelium. Perlecan down‐regulation in cultured keratinocytes caused depletion of the cell population that expressed keratin 15. This phenomenon depended on the perlecan heparan sulphate moieties, which suggested the involvement of a growth factor. Finally, we found defects in keratin 15 expression in the epidermis of aging skin. This study highlighted a new role for perlecan in maintaining the self‐renewal capacity of basal keratinocytes.


DEJ: dermal-epidermal junction; ECM: dermalextracellular matrix; BM: basement membrane; HSPG: heparan sulfate proteoglycan; NHK: normal human keratinocytes; SE: skin equivalent; DE: dermal equivalent.