Journal
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
Volume 65, Issue 11, Pages 1165-1180Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/gerona/glq129
Keywords
TL1A; HUVEC; CEP; Senescence; Ectodomain shedding
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Funding
- Austrian Science Fund (Fonds zur Forderung der wissenschaftlichen Forschung-National Research Network) [S93]
- European Community [LSHM-CT-2005-518230]
- Austrian Federal Ministry of Science and Research
- Austrian Science Fund (FWF) [S93] Funding Source: Austrian Science Fund (FWF)
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Tumor necrosis factor-like cytokine 1A (TL1A) is expressed in endothelial cells and contributes to T-cell activation, via an extracellular fragment TL1A(L72-L251), generated by ectodomain shedding. Fragments of TL1A, referred to as vascular endothelial growth inhibitor, were found to induce growth arrest and apoptosis in endothelial cells; however, the underlying mechanisms remained obscure. Here, we show that full-length TL1A is the major detectable gene product in both human umbilical vein endothelial cells and circulating endothelial progenitor cells. TL1A expression was significantly enhanced in senescent circulating endothelial progenitor cells, and knockdown of TL1A partially reverted senescence. TL1A overexpression induced premature senescence in both circulating endothelial progenitor cells and human umbilical vein endothelial cells. We also identified a novel extracellular fragment of TL1A, TL1A(V84-L251), resulting from differential ectodomain shedding, which induced growth arrest and apoptosis in human umbilical vein endothelial cells. These findings suggest that TL1A is involved in the regulation of endothelial cell senescence, via a novel fragment produced by differential ectodomain shedding.
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