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 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.
Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Maki
M
Kaneko
Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Takeo
T
Minematsu
Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Mikako
M
Yoshida
Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yoshimi
Y
Nishijima
Department of Life Support Technology (Molten), Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Hiroshi
H
Noguchi
Department of Pathology, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Yasunori
Y
Ohta
Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Gojiro
G
Nakagami
Department of Life Support Technology (Molten), Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Taketoshi
T
Mori
Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Hiromi
H
Sanada
D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000235:genetics*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D011312:Pressure; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D058258:Serpin E2 / Q000096:biosynthesis / Q000235:genetics*; D012867:Skin / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D013314:Stress, Mechanical; D013927:Thrombosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D014945:Wound Healing; D014947:Wounds and Injuries / Q000150:complications / Q000235:genetics* / Q000378:metabolism
C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D058258:Serpin E2; C511869:Serpine2 protein, mouse
hypoxia; hypoxia-inducible factor-1; plasminogen activator inhibitor-1; pressure ulcer; thrombus