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15(S)‐Hydroxyeicosatetraenoic acid‐induced angiogenesis requires Src‐mediated Egr‐1‐dependent rapid induction of FGF‐2 expression
Author(s) -
KundumaniSridharan Venkatesh,
Niu Jixiao,
Wang Dong,
Van Quyen Dong,
Zhang Qiuhua,
Subramani Jaganathan,
Karri Saradasri,
Rao Gadiparthi N
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1031.3
Subject(s) - angiogenesis , matrigel , chemistry , fibroblast growth factor , proto oncogene tyrosine protein kinase src , microbiology and biotechnology , biology , cancer research , biochemistry , signal transduction , receptor
To understand the mechanisms underlying 15(S)‐hydroxyeicosatetraenoic acid (15(S)‐HETE)‐induced angiogenesis, we have studied the role of Egr‐1. 15(S)‐HETE induced Egr‐1 expression in a time dependent manner in HDMVECs. Blockade of Egr‐1 via forced expression of its dominant negative mutant attenuated 15(S)‐HETE‐induced HDMVEC migration and tube formation as well as Matrigel plug angiogenesis. 15(S)‐HETE‐induced Egr‐1 expression requires Src activation. In addition, adenovirus‐mediated expression of dominant negative mutant of Src blocked 15(S)‐HETE's effects on migration and tube formation of HDMVECs and Matrigel plug angiogenesis. 15(S)‐HETE induced FGF‐2 expression rapidly via Src‐mediated production of Egr‐1. Cloning and mutational analysis of FGF‐2 promoter revealed that Egr‐1 binding site proximal to transcription start site is required for 15(S)‐HETE‐induced FGF‐2 expression. Neutralizing antibody‐mediated suppression of FGF‐2 function also attenuated the effects of 15(S)‐HETE on HDMVEC migration and tube formation as well as Matrigel plug angiogenesis. Furthermore, in contrast to WT mice, 12/15‐LOX−/− mice exhibited decreased Matrigel plug angiogenesis in response to AA. Based on these observations, we conclude that 15(S)‐HETE‐induced angiogenesis requires Src‐mediated Egr‐1‐dependent rapid induction of FGF‐2.