Compression-induced HIF-1 enhances thrombosis and PAI-1 expression in mouse skin

Maki Kaneko, Takeo Minematsu, Mikako Yoshida, Yoshimi Nishijima, Hiroshi Noguchi, Yasunori Ohta, Gojiro Nakagami, Taketoshi Mori, Hiromi Sanada

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Pressure ulcers result from tissue hypoxia caused by external forces. Thrombosis due to external forces is considered important, and hypoxia inducible factor-1 (HIF-1) is a master regulator of pressure ulcer development. To date, however, their causal relationship has not been determined. This study therefore investigated the mutual relationship between thrombosis and HIF-1 activation in compressed mouse skin, based on a hypothesis that HIF-1 regulation by plasminogen activator inhibitor-1 (PAI-1) enhances thrombosis. Compression of mouse skin significantly increased the numbers of thrombi and HIF-1α-positive cells compared with control skin. A thrombosis inhibitor significantly reduced the numbers of HIF-1α-positive cells and an HIF-1 inhibitor significantly inhibited thrombosis in compressed skin tissue, suggesting a mutual relationship between thrombosis and HIF-1 activation. Compression of mouse skin also enhanced the level of Pai-1 messenger RNA expression, but this increase was significantly reduced by treatment with an HIF-1 inhibitor, whereas a thrombosis inhibitor had no effect. These results suggested the involvement of PAI-1 in HIF-1-enhanced thrombosis and that an additional factor participates in regulating Pai-1 expression in compressed skin. These findings may suggest new strategies in pressure ulcer management.

Original languageEnglish
Pages (from-to)657-663
Number of pages7
JournalWound Repair and Regeneration
Issue number5
Publication statusPublished - 2015 Sep 1
Externally publishedYes


  • hypoxia
  • hypoxia-inducible factor-1
  • plasminogen activator inhibitor-1
  • pressure ulcer
  • thrombus

ASJC Scopus subject areas

  • Surgery
  • Dermatology

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