Apoptosis of human endothelial cells is accompanied by proteolytic processing of latent TGF-β binding proteins and activation of TGF-β

Transforming growth factors beta (TGF-beta s) are multifunctional cytokines that modulate cell growth, differentiation and apoptosis. Numerous effects initiated by TGF-beta s in vitro have been described, but the role of TGF-beta targeting and activation under physiological conditions has gained very little attention and understanding. We report here that apoptosis of human umbilical vein endothelial cells (HUVECs) is accompanied by release of truncated large latent TGF-beta complexes from the pericellular matrix followed by activation of TGF-beta. The activation of TGF-beta during apoptosis was accompanied by enhanced secretion of beta 1-LAP protein, and apoptotic HUVECs acquired the capacity to induce the release of latent TGF-beta-binding proteins (LTBPs) from extracellular matrices. Activated TGF-beta, in turn, attenuated apoptotic death of HUVECs. Current results indicate that the activation of TGF-beta accompanies the apoptosis of HUVECs, and may play a protective feedback role against apoptotic cell death. The results suggest a role for TGF-beta as a putative extracellular modulator of apoptosis.