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01.03.2014 | Original Article—Alimentary Tract

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

verfasst von: Takehito Sato, Hideki Amano, Yoshiya Ito, Koji Eshima, Tsutomu Minamino, Takako Ae, Chikatoshi Katada, Takashi Ohno, Kanako Hosono, Tatsunori Suzuki, Masabumi Shibuya, Wasaburo Koizumi, Masataka Majima

Erschienen in: Journal of Gastroenterology | Ausgabe 3/2014

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

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Titel: 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
verfasst von: Takehito Sato
Hideki Amano
Yoshiya Ito
Koji Eshima
Tsutomu Minamino
Takako Ae
Chikatoshi Katada
Takashi Ohno
Kanako Hosono
Tatsunori Suzuki
Masabumi Shibuya
Wasaburo Koizumi
Masataka Majima
Publikationsdatum: 01.03.2014
Verlag: Springer Japan
Erschienen in: Journal of Gastroenterology / Ausgabe 3/2014
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI: https://doi.org/10.1007/s00535-013-0869-z

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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

Abstract

Background

Methods

Results

Conclusion

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Abstract

Background

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