title: Hyperpigmentation in human solar lentigo is promoted by heparanase-induced loss of heparan sulfate chains at the dermal-epidermal junction.
abstract: BACKGROUND
  Skin pigmentation induced by ultraviolet B radiation is caused in part by inflammation mediated by cytokines secreted from keratinocytes and fibroblasts in the irradiated area. Heparanase is also activated in the irradiated skin, and this leads to loss of heparan sulfate at the dermal-epidermal junction (DEJ), resulting in uncontrolled diffusion of heparan sulfate-binding cytokines through the DEJ. However, it is not clear whether heparanase-induced loss of heparan sulfate at the DEJ is involved in the pigmentation process in sun-exposed skin.
  
  
  OBJECTIVE
  We examined the role of heparan sulfate in the pigmentation process of human pigmented skin and in pigmented skin-equivalent model.
  
  
  METHODS
  Heparan sulfate and blood vessels in human pigmented skin, solar lentigo, and non-pigmented skin were evaluated by means of immunohistochemistry. Pigmented skin equivalent models were cultured with or without heparanase inhibitor and the pigmentation levels were compared.
  
  
  RESULTS
  In solar lentigo, heparan sulfate was hardly observed, presumably due to the increase of heparanase at the DEJ, in spite of the deposition of core protein of perlecan (also known as heparan sulfate proteoglycan). The number of blood vessels was significantly increased in solar lentigo. In the pigmented skin equivalent model, heparanase inhibitor increased the staining intensity of heparan sulfate at the DEJ and markedly reduced melanogenesis in the epidermis.
  
  
  CONCLUSIONS
  Our results indicate that heparanase-induced loss of heparan sulfate at the DEJ is involved in the pigmentation process of human skin. Consequently, heparanase inhibitors can be expected to exert a protective effect against ultraviolet exposure-induced skin pigmentation.
authors: Shiseido Research Center, 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama 224-8558, Japan. shunsuke.iriyama@to.shiseido.co.jp
authors: Shunsuke
authors: S
authors: Iriyama
authors: Takayuki
authors: T
authors: Ono
authors: Hirofumi
authors: H
authors: Aoki
authors: Satoshi
authors: S
authors: Amano
mesh_terms: D000328:Adult; D001706:Biopsy; D016207:Cytokines / Q000378:metabolism; D020405:Dermis / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology / Q000528:radiation effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology / Q000528:radiation effects; D005966:Glucuronidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007911:Lentigo / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D008297:Male; D008543:Melanins / Q000378:metabolism; D008875:Middle Aged; D012880:Skin Pigmentation / Q000187:drug effects / Q000528:radiation effects; D013472:Sunlight / Q000009:adverse effects; D013997:Time Factors; D046509:Tissue Culture Techniques; D000099175:Heparanase
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; D005966:Glucuronidase; D019812:Heparan Sulfate Proteoglycans; D008543:Melanins; D000099175:Heparanase; C071927:perlecan