Endothelial cell regulation by transforming growth factor-beta.
Pronounced changes including growth inhibition, increased matrix deposition and suppression of cell-associated proteolytic activity, take place in endothelial cells (EC) upon the application of TGF-beta. Interrelationships between these effects have shed some light on the mechanism of action of TGF-beta and on its role in regulating EC function vis-a-vis angiogenesis. For instance, preliminary evidence has indicated that increased levels of certain matrix components may be partly responsible for the antiproliferative action of TGF-beta. In addition, TGF-beta and bFGF have opposing effects on cellular proteolytic balance which may contribute to the antagonistic effect that TGF-beta has on bFGF-induced EC growth and possibly to the anti-angiogenic effect exerted by TGF-beta under certain circumstances. Of particular interest in this regard is the fact that physical contact between EC and vascular mural cells in EC:mural cell cocultures has been found to generate active TGF-beta, thus further implicating TGF-beta in the maintenance of the quiescent, differentiated aggregation of EC as found in vascular structures in vivo. While more information is needed to define what, if any role TGF-beta plays in endothelial differentiation, it is to be noted that many of the cellular and biochemical processes affected by TGF-beta are linked to differentiation. It is therefore possible that the growth inhibition of EC by TGF-beta primes them for differentiation and/or is critical for the maintenance of a differentiated state.
RayChaudhury
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A
Laboratory for Surgical Research, Children's Hospital, Boston, Massachusetts.
D'Amore
P A
PA
D000818:Animals; D002454:Cell Differentiation; D004730:Endothelium, Vascular / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D009389:Neovascularization, Pathologic; D010958:Plasminogen / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*
D016212:Transforming Growth Factor beta; D010958:Plasminogen