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

Abstract

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.

• Authors: Maki Kaneko, Takeo Minematsu, Mikako Yoshida, Yoshimi Nishijima, Hiroshi Noguchi, Yasunori Ohta, Gojiro Nakagami, Taketoshi Mori, Hiromi Sanada
• Journal: Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society (Wound Repair Regen) Vol. 23 Issue 5 Pg. 657-63 (Sep 2015) ISSN: 1524-475X [Electronic] United States
• PMID: 25939592 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by the Wound Healing Society.

Chemical References

• Hif1a protein, mouse
• Hypoxia-Inducible Factor 1, alpha Subunit
• RNA, Messenger
• Serpin E2
• Serpine2 protein, mouse

Topics

• Animals
• Disease Models, Animal
• Gene Expression Regulation
• Hypoxia-Inducible Factor 1, alpha Subunit (biosynthesis, genetics)
• Immunohistochemistry
• Male
• Mice
• Pressure
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Serpin E2 (biosynthesis, genetics)
• Skin (injuries, metabolism, pathology)
• Stress, Mechanical
• Thrombosis (etiology, genetics, metabolism)
• Wound Healing
• Wounds and Injuries (complications, genetics, metabolism)