Fatty acid binding protein 4 is a target of VEGF and a regulator of cell proliferation in endothelial cells.
Fatty acid binding protein 4 (FABP4) plays an important role in maintaining glucose and lipid homeostasis. FABP4 has been primarily regarded as an adipocyte- and macrophage-specific protein, but recent studies suggest that it may be more widely expressed. We found strong FABP4 expression in the endothelial cells (ECs) of capillaries and small veins in several mouse and human tissues, including the heart and kidney. FABP4 was also detected in the ECs of mature human placental vessels and infantile hemangiomas, the most common tumor of infancy and ECs. In most of these cases, FABP4 was detected in both the nucleus and cytoplasm. FABP4 mRNA and protein levels were significantly induced in cultured ECs by VEGF-A and bFGF treatment. The effect of VEGF-A on FABP4 expression was inhibited by chemical inhibition or short-hairpin (sh) RNA-mediated knockdown of VEGF-receptor-2 (R2), whereas the VEGFR1 agonists, placental growth factors 1 and 2, had no effect on FABP4 expression. Knockdown of FABP4 in ECs significantly reduced proliferation both under baseline conditions and in response to VEGF and bFGF. Thus, FABP4 emerged as a novel target of the VEGF/VEGFR2 pathway and a positive regulator of cell proliferation in ECs.
Elmasri
Harun
H
Division of Newborn Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
Karaaslan
Cagatay
C
Teper
Yaroslav
Y
Ghelfi
Elisa
E
Weng
Meiqian
M
Ince
Tan A
TA
Kozakewich
Harry
H
Bischoff
Joyce
J
Cataltepe
Sule
S
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D006391:Hemangioma / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000166:cytology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D042442:Vascular Endothelial Growth Factors / Q000502:physiology*
C493410:FABP4 protein, human; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2