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

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...

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Bibliographic Details
Published in:Wound repair and regeneration 2015-09, Vol.23 (5), p.657-663
Main Authors: Kaneko, Maki, Minematsu, Takeo, Yoshida, Mikako, Nishijima, Yoshimi, Noguchi, Hiroshi, Ohta, Yasunori, Nakagami, Gojiro, Mori, Taketoshi, Sanada, Hiromi
Format: Article
Language:English
Subjects:
Animals
Disease Models, Animal
Gene Expression Regulation
hypoxia
Hypoxia-Inducible Factor 1, alpha Subunit - biosynthesis
Hypoxia-Inducible Factor 1, alpha Subunit - genetics
hypoxia‐inducible factor‐1
Immunohistochemistry
Male
Mice
plasminogen activator inhibitor‐1
Pressure
pressure ulcer
Real-Time Polymerase Chain Reaction
RNA, Messenger - genetics
Serpin E2 - biosynthesis
Serpin E2 - genetics
Skin - injuries
Skin - metabolism
Skin - pathology
Stress, Mechanical
Thrombosis - etiology
Thrombosis - genetics
Thrombosis - metabolism
thrombus
Wound Healing
Wounds and Injuries - complications
Wounds and Injuries - genetics
Wounds and Injuries - metabolism
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Summary: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.
ISSN:1067-1927
1524-475X
DOI:10.1111/wrr.12312