PMID- 26323829 OWN - NLM STAT- MEDLINE DCOM- 20160808 LR - 20220409 IS - 1791-2431 (Electronic) IS - 1021-335X (Linking) VI - 34 IP - 5 DP - 2015 Nov TI - Hypoxia-induced fibroblast growth factor 11 stimulates capillary-like endothelial tube formation. PG - 2745-51 LID - 10.3892/or.2015.4223 [doi] AB - 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. FAU - Yang, Jimin AU - Yang J AD - Biomedical Research Institute and IRICT, Seoul National University Hospital, Seoul, Republic of Korea. FAU - Kim, Woo Jean AU - Kim WJ AD - National Research Laboratory of Regenerative Sexual Medicine, Department of Urology, Inha University School of Medicine, Incheon, Republic of Korea. FAU - Jun, Hyoung Oh AU - Jun HO AD - Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea. FAU - Lee, Eun Ju AU - Lee EJ AD - Biomedical Research Institute and IRICT, Seoul National University Hospital, Seoul, Republic of Korea. FAU - Lee, Kyeong Won AU - Lee KW AD - Marine Biotechnology Research Group, Korea Institute of Ocean Science and Technology, Ansan, Republic of Korea. FAU - Jeong, Jae-Yeon AU - Jeong JY AD - Marine Biotechnology Research Group, Korea Institute of Ocean Science and Technology, Ansan, Republic of Korea. FAU - Lee, Sae-Won AU - Lee SW AD - Biomedical Research Institute and IRICT, Seoul National University Hospital, Seoul, Republic of Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150824 PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (CLDN5 protein, human) RN - 0 (Claudin-5) RN - 0 (FGF11 protein, human) RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (TJP1 protein, human) RN - 0 (Zonula Occludens-1 Protein) RN - 62031-54-3 (Fibroblast Growth Factors) SB - IM MH - Binding Sites MH - Cell Hypoxia MH - Cell Movement MH - Claudin-5/metabolism MH - Endothelial Cells/*cytology/metabolism MH - Fibroblast Growth Factors/chemistry/*genetics/*metabolism MH - HEK293 Cells MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism MH - Promoter Regions, Genetic MH - Up-Regulation MH - Zonula Occludens-1 Protein/metabolism EDAT- 2015/09/02 06:00 MHDA- 2016/08/09 06:00 CRDT- 2015/09/02 06:00 PHST- 2015/06/04 00:00 [received] PHST- 2015/07/06 00:00 [accepted] PHST- 2015/09/02 06:00 [entrez] PHST- 2015/09/02 06:00 [pubmed] PHST- 2016/08/09 06:00 [medline] AID - 10.3892/or.2015.4223 [doi] PST - ppublish SO - Oncol Rep. 2015 Nov;34(5):2745-51. doi: 10.3892/or.2015.4223. Epub 2015 Aug 24.