The expanding role of neuropilin: regulation of transforming growth factor-β and platelet-derived growth factor signaling in the vasculature

Abstract

Purpose of review: Long recognized for its role in regulation of vascular endothelial growth factor signaling, neuropilin (Nrp)1 has emerged as a modulator of additional signaling pathways critical for vascular development and function. Here we review two novel functions of Nrp1 in blood vessels: regulation of transforming growth factor-β (TGFβ) signaling in endothelial cells and regulation of platelet-derived growth factor (PDGF) signaling in vascular smooth muscle cells.

Recent findings: Novel mouse models demonstrate that Nrp1 fulfills vascular functions independent of vascular endothelial growth factor signaling. These include modulation of TGFβ-dependent inhibition of endothelial sprouting during developmental angiogenesis and PDGF signaling in vascular smooth muscle cells during development and disease.

Summary: Broadening our understanding of how and where Nrp1 functions in the vasculature is critical for the development of targeted therapeutics for cancer and vascular diseases such as atherosclerosis and retinopathies.

Figure 1. Nrp1 modulation of the endothelial tip cell phenotype

(A) In tip cells, Nrp1 promotes endothelial sprouting by enhancing VEGFR2 signaling. (B) Canonical TGFβ signaling inhibits endothelial cell sprouting and promotes the stalk cell phenotype. In tip cells, Nrp1 inhibits TGFβ signaling.