Vascular endothelial growth factor receptor 1 signaling facilitates gastric ulcer healing and angiogenesis through the upregulation of epidermal growth factor expression on VEGFR1+CXCR4+ cells recruited from bone marrow
| Autor: | Wasaburo Koizumi, Takehito Sato, Tsutomu Minamino, Hideki Amano, Chikatoshi Katada, Kanako Hosono, Masataka Majima, Takashi Ohno, Takako Ae, Masabumi Shibuya, Koji Eshima, Yoshiya Ito, Tatsunori Suzuki |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Receptors CXCR4 animal structures Angiogenesis Neovascularization Physiologic Bone Marrow Cells Fibroblast growth factor Neovascularization Mice Downregulation and upregulation Epidermal growth factor medicine Animals Stomach Ulcer Bone Marrow Transplantation Mice Knockout Vascular Endothelial Growth Factor Receptor-1 Epidermal Growth Factor business.industry Gastroenterology digestive system diseases Up-Regulation Mice Inbred C57BL body regions Disease Models Animal medicine.anatomical_structure Vascular endothelial growth factor C Immunology cardiovascular system Cancer research Bone marrow Signal transduction medicine.symptom business Signal Transduction |
| Zdroj: | Journal of Gastroenterology. 49:455-469 |
| ISSN: | 1435-5922 0944-1174 |
| DOI: | 10.1007/s00535-013-0869-z |
| Popis: | Angiogenesis is essential for gastric ulcer healing. Recent results suggest that vascular endothelial growth factor receptor 1 (VEGFR1), which binds to VEGF, promotes angiogenesis. In the present study, we investigated the role of VEGFR1 signaling in gastric ulcer healing and angiogenesis.Gastric ulcers were induced by serosal application of 100 % acetic acid in wild-type (WT) and tyrosine kinase-deficient VEGFR1 mice (VEGFR1 TK(-/-)). Bone marrow transplantation into irradiated WT mice was carried out using bone marrow cells isolated from WT and VEGFR1 TK(-/-) mice.Ulcer healing was delayed in VEGFR1 TK(-/-) mice compared to WT mice and this was accompanied by decreased angiogenesis, as evidenced by reduced mRNA levels of CD31 and decreased microvessel density. Recruitment of cells expressing VEGFR1 and C-X-C chemokine receptor type 4 (CXCR4) was suppressed and epidermal growth factor (EGF) expression in ulcer granulation tissue was attenuated. Treatment of WT mice with neutralizing antibodies against VEGF or CXCR4 also delayed ulcer healing. In WT mice transplanted with bone marrow cells from VEGFR1 TK(-/-) mice, ulcer healing and angiogenesis were suppressed, and this was associated with reduced recruitment of bone marrow cells to ulcer granulation tissue. VEGFR1 TK(-/-) bone marrow chimeras also exhibited downregulation of EGF expression on CXCR4(+)VEGFR1(+) cells recruited from the bone marrow into ulcer lesions.VEGFR1-mediated signaling plays a critical role in gastric ulcer healing and angiogenesis through enhanced EGF expression on VEGFR1(+)CXCR4(+) cells recruited from the bone marrow into ulcer granulation tissue. |
| Databáze: | OpenAIRE |
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