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VEGF‐A induces its negative regulator, soluble form of VEGFR‐1, by modulating its alternative splicing
Author(s) -
Saito Tetsuya,
Takeda Norihiko,
Amiya Eisuke,
Nakao Tomoko,
Abe Hajime,
Semba Hiroaki,
Soma Katsura,
Koyama Katsuhiro,
Hosoya Yumiko,
Imai Yasushi,
Isagawa Takayuki,
Watanabe Masafumi,
Manabe Ichiro,
Komuro Issei,
Nagai Ryozo,
Maemura Koji
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.05.038
Subject(s) - angiogenesis , vascular endothelial growth factor , regulator , downregulation and upregulation , alternative splicing , vegf receptors , microbiology and biotechnology , chemistry , cancer research , kinase insert domain receptor , signal transduction , kinase , receptor , vascular endothelial growth factor a , gene , biology , biochemistry , messenger rna
Vascular endothelial growth factor‐A (VEGF‐A) is one of the major angiogenic factors, and its actions are primarily mediated through its two membrane receptors, VEGFR‐1 and VEGFR‐2. A soluble form of VEGFR‐1 (sVEGFR‐1) sequesters the free form of VEGF‐A, and acts as a potent anti‐angiogenic factor. While sVEGFR‐1 is synthesized as a splice variant of VEGF‐R1 gene, the interactions between VEGF‐A and sVEGFR‐1 remain largely unknown. Here, we show that VEGF‐A upregulates sVEGF‐R1 expression in human vascular endothelial cells but leaves full‐length VEGF‐R1 expression unchanged, and that this induction was dependent on the VEGFR‐2‐protein kinase C‐MEK signaling pathway. The VEGF‐A‐induced sVEGFR‐1 upregulation can operate as a negative feedback system, which if modulated can become a novel therapeutic target for regulating pathological angiogenesis.