Thrombospondin-4 mediates TGF-beta-induced angiogenesis.

Thrombospondin-4 mediates TGF-beta-induced angiogenesis.

Muppala S; Xiao R; Krukovets I; Verbovetsky D; Yendamuri R; Habib N; Raman P; Plow E; Stenina-Adognravi O

Oncogene

2017

2017-09

TGF-beta is a multifunctional cytokine affecting many cell types and implicated in tissue remodeling processes. Due to its many functions and cell-specific effects, the consequences of TGF-beta signaling are process-and stage-dependent, and it is not uncommon that TGF-beta exerts distinct and sometimes opposing effects on a disease progression depending on the stage and on the pathological changes associated with the stage. The mechanisms underlying cell- and process-specific effects of TGF-beta are poorly understood. We are describing a novel pathway that mediates induction of angiogenesis in response to TGF-beta1. We found that in endothelial cells (EC) thrombospondin-4 (TSP-4), a secreted extracellular matrix (ECM) protein, is upregulated in response to TGF-beta1 and mediates the effects of TGF-beta1 on angiogenesis. Upregulation of TSP-4 does not require the synthesis of new protein, is not caused by decreased secretion of

Angiogenesis Inducing Agents/*metabolism; Animals; Cell Movement/drug effects; Cell Proliferation/drug effects; Cells; Chick Embryo; Cultured; Endothelium; Female; Gene Expression Regulation/drug effects; Humans; Inbred C57BL; Male; Mice; Muscle; Neovascularization; Pathologic/drug therapy/metabolism/*pathology; Signal Transduction/drug effects; Smooth; Thrombospondins/*physiology; Transforming Growth Factor beta/*pharmacology; Vascular/drug effects/metabolism/*pathology

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