Regulation of Foxo-1 and the angiopoietin-2/Tie2 system by shear stress.
Transcription factor Foxo-1 can be inactivated via Akt-mediated phosphorylation. Since shear stress activates Akt, we determined whether Foxo-1 and the Foxo-1-dependent, angiogenesis-related Ang-2/Tie2-system are influenced by shear stress in endothelial cells. Expression of Foxo-1 and its target genes p27Kip1 and Ang-2 was decreased under shear stress (6dyn/cm(2), 24h), nuclear exclusion of Foxo-1 by phosphorylation increased. eNOS and Tie2 were upregulated. No effects on Ang-1 expression were detected. In conclusion, Foxo-1 and Ang-2/Tie2 are part of the molecular response to shear stress, which may regulate angiogenesis.
Chlench
Sven
S
Charité, Campus Benjamin Franklin, Institute of Physiology, Arnimallee 22, 14195 Berlin, Germany.
Mecha Disassa
Nigussie
N
Hohberg
Margret
M
Hoffmann
Christian
C
Pohlkamp
Theresa
T
Beyer
Gabriele
G
Bongrazio
Mauro
M
Da Silva-Azevedo
Luis
L
Baum
Oliver
O
Pries
Axel Radlach
AR
Zakrzewicz
Andreas
A
D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism; D042702:Angiopoietin-2 / Q000235:genetics* / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000235:genetics* / Q000378:metabolism*; D013314:Stress, Mechanical; D013997:Time Factors
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D002867:Chromones; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D042787:Receptor, TIE-2; D051057:Proto-Oncogene Proteins c-akt