Solovyan V T, Keski-Oja J
Departments of Pathology and Virology, Haartman Institute, University of Helsinki, Biomedicum Helsinki and Helsinki University Hospital, FIN-00014 Helsinki, Finland.
Cell Death Differ. 2005 Jul;12(7):815-26. doi: 10.1038/sj.cdd.4401618.
Transforming growth factors beta (TGF-betas) are multifunctional cytokines that modulate cell growth, differentiation and apoptosis. Numerous effects initiated by TGF-betas 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 beta1-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.
转化生长因子β（TGF-βs）是调节细胞生长、分化和凋亡的多功能细胞因子。TGF-βs在体外引发的众多效应已有描述，但在生理条件下TGF-β的靶向作用和激活作用却很少受到关注和研究。我们在此报告，人脐静脉内皮细胞（HUVECs）凋亡伴随着截短的大潜伏TGF-β复合物从细胞周围基质中释放，随后TGF-β被激活。凋亡过程中TGF-β的激活伴随着β1-LAP蛋白分泌增加，凋亡的HUVECs获得了从细胞外基质诱导释放潜伏TGF-β结合蛋白（LTBPs）的能力。反过来，激活的TGF-β减弱了HUVECs的凋亡性死亡。目前的结果表明，TGF-β的激活伴随着HUVECs的凋亡，并可能对凋亡性细胞死亡起到保护性反馈作用。这些结果提示TGF-β作为一种假定的细胞外凋亡调节剂发挥作用。
