VEGF-VEGFR System as a Target for Suppressing Inflammation and other Diseases

Endocrine, Metabolic & Immune Disorders Drug Targets
Masabumi Shibuya

Abstract

The vascular endothelial growth factor (VEGF)-VEGF receptor (R) system is deeply involved in angiogenesis and lymphangiogenesis. VEGFR1/ Fms-like tyrosine kinase-1 (Flt-1) and VEGFR2 are significantly expressed in vascular endothelial cells, where they transfer proangiogenic signals. Particularly, VEGFR2 has strong tyrosine kinase activity; thus, the major and direct angiogenic signals are generated from VEGFR2. VEGFR3 is specifically expressed in lymphatic endothelial cells, generating the main signal for lymphangiogenesis. In addition, VEGFR1 is wellexpressed on the membrane of macrophage lineage cells such as monocytes, transducing an important signal for the migration and cytokine/chemokine production of these cells. This VEGFR1-macrophage axis stimulates seemingly non-inflammatory and inflammatory responses in various tissues and promotes a variety of diseases such as tumor growth via proangiogenesis, tumor metastasis, lymphangiogenesis, arthritis, and atherosclerosis. This axis is also important for the physiological recovery systems like bone marrow reconstitution and wound healing. VEGFR1 expresses two forms of mRNA: one for the full-length VEGFR1/Flt-1 receptor with tyrosine kinase; the other for a soluble form carryin...Continue Reading

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