Extracellular control of TGFbeta signalling in vascular development and disease.
The intracellular mechanism of transforming growth factor-beta (TGFbeta) signalling via kinase receptors and SMAD effectors is firmly established, but recent studies of human cardiovascular syndromes such as Marfan syndrome and pre-eclampsia have refocused attention on the importance of regulating the availability of active extracellular TGFbeta. It seems that elastic extracellular matrix (ECM) components have a crucial role in controlling TGFbeta signalling, while soluble and membrane bound forms of TGFbeta co-receptors add further layers of regulation. Together, these extracellular interactions determine the final bioavailability of TGFbeta to vascular cells, and dysregulation is associated with an increasing number of vascular pathologies.
ten Dijke
Peter
P
Molecular Cell Biology, Leiden University Medical Center, Postbus 9600, 2300 RC Leiden, The Netherlands. p.ten_dijke@lumc.nl
Arthur
Helen M
HM
D000818:Animals; D001808:Blood Vessels / Q000196:embryology* / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014652:Vascular Diseases / Q000378:metabolism*
D016212:Transforming Growth Factor beta