Hypoxia-induced fibroblast growth factor 11 stimulates capillary-like endothelial tube formation.

Abstract

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.

• Authors: Jimin Yang, Woo Jean Kim, Hyoung Oh Jun, Eun Ju Lee, Kyeong Won Lee, Jae-Yeon Jeong, Sae-Won Lee
• Journal: Oncology reports (Oncol Rep) Vol. 34 Issue 5 Pg. 2745-51 (Nov 2015) ISSN: 1791-2431 [Electronic] Greece
• PMID: 26323829 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CLDN5 protein, human
• Claudin-5
• FGF11 protein, human
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• TJP1 protein, human
• Zonula Occludens-1 Protein
• Fibroblast Growth Factors

Topics

• Binding Sites
• Cell Hypoxia
• Cell Movement
• Claudin-5 (metabolism)
• Endothelial Cells (cytology, metabolism)
• Fibroblast Growth Factors (chemistry, genetics, metabolism)
• HEK293 Cells
• Human Umbilical Vein Endothelial Cells
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Promoter Regions, Genetic
• Up-Regulation
• Zonula Occludens-1 Protein (metabolism)