Hypoxia-induced fibroblast growth factor 11 stimulates capillary-like endothelial tube formation.
Low oxygen or hypoxia can be observed in the central region of solid tumors. Hypoxia is a strong stimulus for new blood vessel formation or angiogenesis, which is essential for tumor growth and progression. Fibroblast growth factor 11 (FGF11) is an intracellular non-secretory FGF whose function has not yet been fully characterized. In the present study, we demonstrated that FGF11 expression is upregulated under hypoxic conditions in human umbilical vein endothelial cells (HUVECs). FGF11 overexpression stimulated capillary-like tube formation, yet did not affect cell migration. Notably, FGF11 markedly increased the levels of tight junction proteins including occludin, zonula occludens-1 (ZO-1) and claudin-5 in HUVECs. The FGF11 promoter contains hypoxia response elements (HREs), and hypoxia-inducible factor-1 (HIF-1) binds to HREs to activate hypoxia-related genes. We demonstrated that hypoxia or HIF-1 expression under normoxic conditions increased the luciferase activity driven by the FGF11 promoter. However, deletion of the HREs from the FGF11 promoter rendered reporter gene activity unresponsive to hypoxia or HIF-1. Taken together, we propose that FGF11 may be involved in the stabilization of capillary-like tube structures associated with angiogenesis and may act as a modulator of hypoxia-induced pathological processes such as tumorigenesis.
Biomedical Research Institute and IRICT, Seoul National University Hospital, Seoul, Republic of Korea.
Jimin
J
Yang
National Research Laboratory of Regenerative Sexual Medicine, Department of Urology, Inha University School of Medicine, Incheon, Republic of Korea.
Woo Jean
WJ
Kim
Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Hyoung Oh
HO
Jun
Biomedical Research Institute and IRICT, Seoul National University Hospital, Seoul, Republic of Korea.
Eun Ju
EJ
Lee
Marine Biotechnology Research Group, Korea Institute of Ocean Science and Technology, Ansan, Republic of Korea.
Kyeong Won
KW
Lee
Marine Biotechnology Research Group, Korea Institute of Ocean Science and Technology, Ansan, Republic of Korea.
Jae-Yeon
JY
Jeong
Biomedical Research Institute and IRICT, Seoul National University Hospital, Seoul, Republic of Korea.
Sae-Won
SW
Lee
D001665:Binding Sites; D015687:Cell Hypoxia; D002465:Cell Movement; D062507:Claudin-5 / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D015854:Up-Regulation; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
C107466:CLDN5 protein, human; D062507:Claudin-5; C000609548:FGF11 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D005346:Fibroblast Growth Factors