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Effects of basic fibroblast growth factor on endothelial cells under conditions of simulated microgravity
Author(s) -
Ulbrich Claudia,
Westphal Kriss,
Baatout Sarah,
Wehland Markus,
Bauer Johann,
Flick Burkhard,
Infanger Manfred,
Kreutz Reinhold,
Vadrucci Sonia,
Egli Marcel,
Cogoli Augusto,
Derradji Hanane,
Pietsch Jessica,
Paul Martin,
Grimm Daniela
Publication year - 2008
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21710
Subject(s) - basic fibroblast growth factor , fibronectin , enos , microbiology and biotechnology , transforming growth factor , chemistry , fibroblast , signal transduction , receptor , extracellular matrix , growth factor , medicine , biology , endocrinology , biochemistry , nitric oxide , nitric oxide synthase , in vitro
Fibroblast growth factors interact with appropriate endothelial cell (EC) surface receptors and initiate intracellular signal cascades, which participate in modulating blood vessel growth. EC, upon exposure to basic fibroblast growth factors (bFGFs) undergo profound functional alterations, which depend on their actual sensitivity and involve gene expression and de novo protein synthesis. We investigated the effects of bFGF on signaling pathways of EA.hy926 cells in different environments. EC were cultured under normal gravity (1 g) and simulated microgravity (µg) using a three‐dimensional (3D) clinostat. Microgravity induced early and late apoptosis, extracellular matrix proteins, endothelin‐1 (ET‐1) and TGF‐β 1 expression. Microgravity reduced eNOS mRNA within 24 h. Moreover, a six‐ to eightfold higher amount of IL‐6 and IL‐8 was secreted within 24 h µg. In addition, microgravity induced a duplication of NF‐kappaB p50, while p65 was quadrupled. At 1 g, bFGF application (4 h) reduced ET‐1, TGF‐β 1 and eNOS gene expression. After 24 h, bFGF enhanced fibronectin, VEGF, Flk‐1, Flt‐1, the release of IL‐6, IL‐8, and TGF‐β 1 . Furthermore, bFGF promoted apoptosis, reduced NFkB p50, but enhanced NFkB p65. After 4 h µg, bFGF decreased TGF‐β 1 , eNOS, and ET‐1 gene expression. After 24 h µg, bFGF elevated fibronectin, Flk‐1 and Flt‐1 protein, and reduced IL‐6 and IL‐8 compared with vehicle treated µg cultures. In µg, bFGF enhanced NF‐KappaB p50 by 50%, Bax by 25% and attenuated p65, activation of caspase‐3 and annexin V‐positive cells. bFGF differently changes intracellular signals in ECs depending whether it is applied under microgravity or normal gravity conditions. In microgravity, bFGF contributes to protect the EC from apoptosis. J. Cell. Biochem. 104: 1324–1341, 2008. © 2008 Wiley‐Liss, Inc.