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Archives of Dermatological Research

, Volume 311, Issue 1, pp 45–53 | Cite as

Podoplanin suppresses the cell adhesion of epidermal keratinocytes via functional regulation of β1-integrin

  • Takashi Shibuya
  • Masaru Honma
  • Mizue Fujii
  • Shin Iinuma
  • Akemi Ishida-Yamamoto
Original Paper

Abstract

Epidermal stem cells adhere more efficiently to the extracellular matrix (ECM) than the less adhesive differentiating cells due to their high expression of cell adhesion molecules including β1-integrin. Podoplanin is majorly expressed in the markedly proliferative and differentiating basal cells of the wounded and psoriatic epidermis. This study was designed to reveal podoplanin’s function in human epidermal keratinocytes (HEK) focusing on its interaction with β1-integrin. We analyzed the adhesion and differentiation of HEK in both podoplanin-overexpressing and -knock-down cells, considering their β1-integrin levels. The basal layer of IL-22-treated hyperproliferative reconstituted epidermis cells (simulating basal hyperproliferative psoriatic epidermal basal cells) expressed higher podoplanin levels than the untreated control cells. The adhesiveness of HaCaT cells, which do not express podoplanin, was reduced after the overexpression of podoplanin. HEK with podoplanin overexpression suppressed the cell adhesion to type I collagen (while downregulating β1-integrin functions) and podoplanin silencing augmented it (by increasing active ECM-bound β1-integrin). The increased cell adhesion to type I collagen induced by podoplanin silencing could be reversed by addition of P5D2, a neutralizing antibody against β1-integrin. In the psoriatic epidermis, podoplanin expression was especially upregulated on the rete ridges of the basal cell layer. This expression pattern was inversely correlated with the total/ECM-bound active β1-integrin-expression, which was stronger at the basal cell layer covering the dermal papillae. Our results indicate that podoplanin inhibits the cell ECM attachment by suppressing β1-integrin and initiating HEK differentiation. Podoplanin is presumably involved in the pathogenesis of psoriasis.

Keywords

Psoriasis Epidermis Differentiation Stem cell Therapeutic target 

Notes

Funding

This study was supported in part by a Grant 15K08582 from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was conducted according to the Declaration of Helsinki and the study protocol was approved by the Asahikawa Medical University ethical committee.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Takashi Shibuya
    • 1
  • Masaru Honma
    • 1
  • Mizue Fujii
    • 1
  • Shin Iinuma
    • 1
  • Akemi Ishida-Yamamoto
    • 1
  1. 1.Department of DermatologyAsahikawa Medical UniversityAsahikawaJapan

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