VEGFR1 signaling facilitates diabetic skin wound healing in mice
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概要
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Aims: Signaling of vascular endothelial growth factor receptor 1 (VEGFR1) is suggested to involve in angiogenesis and lymphangiogenesis. The objective of the present study was to examine the role of VEGFR1 signaling in angiogenesis/lymphangiogenesis during diabetic skin wound healing.Methods: VEGFR1-tyrosine kinase knockout mice (KO) or their wild counterparts (WT) were treated with streptozotosin (STZ) or vehicle (Veh). Full-thickness skin wounds were created on the backs of mice.Results: Compared with non-diabetic mice (Veh/WT), wound healing and angiogenesis were suppressed in diabetic mice (STZ/WT) and non-diabetic KO mice (Veh/KO), with reduced expression of VEGF-A and CD31 in wound granulation tissues. Formation of lymphatic vessels was inhibited with reduced expression of VEGF-C, VEGF-D and VEGFR3. Accumulated VEGFR1-positive macrophages with VEGF-C or VEGF-D-expressing cells in granulation tissues were decreased. This was associated with attenuated expression of mannose receptor (MR) and transforming growth factor-beta (TGF β). Diabetic KO (STZ/KO) showed further delayed wound healing and wound-induced angiogenesis/lymphangiogenesis. Exaggerated reduction in recruitment of VEGFR1-positive macrophages and in expression of MR and TGF β was also demonstrated. Conclusions: These results indicate that VEGFR1 signaling plays a role in angiogenesis/lymphangiogenesis through recruitment of VEGFR1-positive macrophages during diabetic wound healing.
- 日本微小循環学会の論文
著者
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Ito Yoshiya
Department Of Cell Biology And Anatomy College Of Medicine University Of Arizona
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Majima Masataka
Department Of Orthopedic Surgery Yokkaichi Municipal Hospital
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Masayoshi Shichiri
Departments of Endocrinology, Kitasato University School of Medicine
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Okubo Hirotoki
Department of Surgery (Vascular Surgery), Saiseikai Yokohamashi Tobu Hospital, Yokohama, Kanagawa, Japan
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Ohba Kazuhito
Departments of Pharmacology, Kitasato University School of Medicine
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Okubo Hirotoki
Departments of Pharmacology, Kitasato University School of Medicine
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Okizaki Shin-ichiro
Departments of Pharmacology, Kitasato University School of Medicine
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Kojyou Ken
Departments of Pharmacology, Kitasato University School of Medicine
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