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Activation of heparanase by ultraviolet B irradiation leads to functional loss of basement membrane at the dermal–epidermal junction in human skin

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Abstract

Recently, we reported that heparanase plays important roles in barrier-disrupted skin, leading to increased interaction of growth factors between epidermis and dermis and facilitating various cutaneous changes, including epidermal hyperplasia and wrinkle formation. However, the role of heparanase in sun-exposed skin remains unknown. Here, we show that heparanase in human keratinocytes is activated by ultraviolet B (UVB) exposure and that heparan sulfate of perlecan is markedly degraded in UVB-irradiated human skin. The degradation of heparan sulfate resulted in a marked reduction of binding activity of the basement membrane for vascular endothelial growth factor, fibroblast growth factor-2 and -7 at the dermal–epidermal junction. Degradation of heparan sulfate was observed not only in acutely UVB-irradiated skin, but also in skin chronically exposed to sun. Interestingly, heparan sulfate was found to be degraded in sun-exposed skin, but not in sun-protected skin. These findings suggest that chronic UVB exposure activates heparanase, leading to degradation of heparan sulfate in the basement membrane and increased growth factor interaction between epidermis and dermis. These changes may facilitate photo-aging.

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Abbreviations

TEWL:

Transepidermal water loss

UVB:

Ultraviolet B

VEGF:

Vascular endothelial growth factor

FGF:

Fibroblast growth factor

HS:

Heparan sulfate

HSPGs:

Heparan sulfate proteoglycans

MED:

Minimal erythema dose

DEJ:

Dermal epidermal junction(s)

MMP:

Matrix metalloproteinase

ATP:

Adenosine triphosphate

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Acknowledgments

We thank Junko Hatori for expert technical assistance.

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Authors and Affiliations

  1. Shiseido Research Center, 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama, 224-8558, Japan

    Shunsuke Iriyama, Yukiko Matsunaga & Satoshi Amano

  2. Department of Dermatology, Iwate Medical University, Morioka, Japan

    Kazuhiro Takahashi

  3. Department of Plastic and Reconstructive Surgery, St. Marianna University School of Medicine, Kawasaki, Japan

    Kyoichi Matsuzaki & Norio Kumagai

Authors
  1. Shunsuke Iriyama
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  2. Yukiko Matsunaga
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  3. Kazuhiro Takahashi
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  4. Kyoichi Matsuzaki
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  5. Norio Kumagai
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  6. Satoshi Amano
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Correspondence to Shunsuke Iriyama.

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Iriyama, S., Matsunaga, Y., Takahashi, K. et al. Activation of heparanase by ultraviolet B irradiation leads to functional loss of basement membrane at the dermal–epidermal junction in human skin. Arch Dermatol Res 303, 253–261 (2011). https://doi.org/10.1007/s00403-010-1117-5

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  • DOI: https://doi.org/10.1007/s00403-010-1117-5

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