Open AccessThrombospondin-1 signaling through CD47 inhibits cell cycle progression and induces senescence in endothelial cells
Author(s) -
Qi Gao,
Kexin Chen,
Lu Gao,
Yang Zheng,
YongGuang Yang
Publication year - 2016
Publication title -
cell death and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.482
H-Index - 111
ISSN - 2041-4889
DOI - 10.1038/cddis.2016.155
Subject(s) - cd47 , senescence , thrombospondin 1 , microbiology and biotechnology , endothelial stem cell , angiogenesis , cell cycle , signal transduction , biology , thrombospondin , cell , cancer research , biochemistry , phagocytosis , metalloproteinase , matrix metalloproteinase , in vitro
CD47 signaling in endothelial cells has been shown to suppress angiogenesis, but little is known about the link between CD47 and endothelial senescence. Herein, we demonstrate that the thrombospondin-1 (TSP1)-CD47 signaling pathway is a major mechanism for driving endothelial cell senescence. CD47 deficiency in endothelial cells significantly improved their angiogenic function and attenuated their replicative senescence. Lack of CD47 also suppresses activation of cell cycle inhibitors and upregulates the expression of cell cycle promoters, leading to increased cell cycle progression. Furthermore, TSP1 significantly accelerates replicative senescence and associated cell cycle arrest in a CD47-dependent manner. These findings demonstrate that TSP1-CD47 signaling is an important mechanism driving endothelial cell senescence. Thus, TSP1 and CD47 provide attractive molecular targets for treatment of aging-associated cardiovascular dysfunction and diseases involving endothelial dysregulation.