کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1995431 1064969 2006 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Enhanced proangiogenic signaling in thrombospondin-1-deficient retinal endothelial cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Enhanced proangiogenic signaling in thrombospondin-1-deficient retinal endothelial cells
چکیده انگلیسی

Thrombospondin-1 (TSP1) is an endogenous inhibitor of angiogenesis, which limits blood vessel density in normal tissues and curtails tumor growth. Previous studies of the molecular and cellular effects of TSP1 in angiogenesis have been contradictory. Here, we show that retinal endothelial cells (REC) prepared from TSP1-deficient (TSP1−/−) mice are more proliferative and migratory compared to the wild type REC. We observed up-regulation of the cell cycle regulators, including cyclin A, D1, and Cdk2, as well as the enhanced sequential activities of Src, PI3-kinase, Akt/PKB, Rac1/Cdc42 GTPases, and p38 MAP kinase in TSP1−/− REC. The increased levels of fibronectin and active Akt/PKB were also observed in retinal vasculature of TSP1−/− mice in vivo. Inhibition of Src/PI3-kinase/P38 MAP kinase activities in TSP1−/− REC resulted in decreased migration. Furthermore, TSP1−/− REC showed decreased intracellular levels of active Fyn and JNK2 without affecting caspase-3 activity. Thus, our results demonstrate that in the absence of TSP1, the proangiogenic signaling is enhanced, possibly through up-regulation of fibronectin expression. The enhanced signaling further promotes EC proliferation, migration, and survival. These novel observations support the TSP1's role as an endogenous inhibitor of angiogenesis whose endothelium expression promotes a quiescent, differentiated phenotype.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Microvascular Research - Volume 71, Issue 3, May 2006, Pages 143–151
نویسندگان
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