Regulation of the expression balance of angiopoietin-1 and angiopoietin-2 by Shh and FGF-2.
Sonic hedgehog (Shh) is a typical morphogen to regulate epithelial-mesenchymal interactions during embryonic development. Shh is also an indirect angiogenic agent upregulating other angiogenic factors, including angiopoietin-1 (Ang-1). Recent studies revealed that angiogenesis induced by Shh is characterized by distinct large-diameter vessels with less branching. Ang-1 promotes blood vessel maturation, and angiopoietin-2 (Ang-2) counteracts Ang-1 activity and regulates vascular branching. Thus, we hypothesized that Shh-induced angiogenesis is affected by expression of Ang-1 and Ang-2, and we investigated the regulatory system of angiopoietins by Shh in vitro. Shh enhanced Ang-1 expression but did not enhance vascular endothelial growth factor in fibroblasts. The upregulation of Ang-1 expression by Shh was significantly decreased by fibroblast growth factor-2 (FGF-2), a potent angiogenic factor. Furthermore, FGF-2 increased the expression of Ang-2 in endothelial cells. These findings suggest that Shh and FGF-2 regulate the expression balance of vascular morphogens Ang-1 and Ang-2 and are involved in angiogenesis.
Fujii
Takaaki
T
Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan. ftakaaki@med.gunma-u.ac.jp
Kuwano
Hiroyuki
H
D042683:Angiopoietin-1 / Q000235:genetics* / Q000378:metabolism; D042702:Angiopoietin-2 / Q000235:genetics* / Q000378:metabolism; D001808:Blood Vessels / Q000254:growth & development; D004730:Endothelium, Vascular / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D053823:Hedgehog Proteins; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2