Pericyte-expressed Tie2 controls angiogenesis and vessel maturation

Area of Science:

• Vascular Biology
• Cell Signaling
• Angiogenesis Research

Background:

• Tie receptors and Angiopoietin ligands are key regulators of angiogenesis and vessel maturation.
• Tie2 receptor signaling is primarily studied in endothelial cells, with its role in pericytes less understood.
• The precise mechanisms by which pericyte Angiopoietin/Tie signaling influences angiogenesis remain unclear.

Purpose of the Study:

• To investigate the functional role of Tie2 receptor expression in pericytes.
• To elucidate the downstream signaling pathways of Tie2 in pericytes.
• To determine the impact of pericyte Tie2 signaling on angiogenesis and tumor growth.

Main Methods:

• Functional assays assessing pericyte migration and sprouting angiogenesis in vitro.
• In vivo spheroid assays and mouse models (Ng2-Cre-driven Tie2 deletion) to study retinal angiogenesis and tumor growth.
• Analysis of Tie2 downstream signaling components including Calpain, Akt, and FOXO3A in pericytes.

Main Results:

• Human and murine pericytes express functional Tie2 receptors.
• Silencing Tie2 in pericytes induced a pro-migratory phenotype and controlled sprouting angiogenesis.
• Pericyte Tie2 deletion in mice transiently delayed retinal angiogenesis but led to enhanced tumor growth.
• Tie2 downstream signaling in pericytes involves Calpain, Akt, and FOXO3A.

Conclusions:

• Pericyte Tie2 signaling is a critical regulator of angiogenesis, distinct from endothelial Tie2.
• Pericyte Tie2 plays a complex role, initially delaying but ultimately promoting angiogenesis in certain contexts like tumor growth.
• These findings propose a revised, bidirectional model of Tie2 signaling involving both endothelial cells and pericytes.