Mutual interaction between endothelial cells and mural cells enhances BMP9 signaling in endothelial cells

Abstract

Hereditary hemorrhagic telangiectasia is characterized by the formation of abnormal vascular networks and caused by the mutation of genes involved in BMP9 signaling. It is also known that the interaction between endothelial cells (ECs) and mural cells (MCs) is critical to maintain vessel integrity. However, it has not yet fully been uncovered whether the EC–MC interaction affects BMP9 signaling or not. To elucidate this point, we analyzed BMP9 signaling in a co-culture of several types of human primary culture ECs and MCs. The co-culture activated the Notch pathway in both types of cells in a co-culture- and BMP9-dependent manner. In HUVECs, the genes induced by BMP9 were significantly and synergistically induced in the presence of pericytes, fibroblasts or mesenchymal stem cells. The synergistic induction was greatly reduced in a non-contact condition. In fibroblasts, PDGFRB expression was potently induced in the presence of HUVECs, and BMP9 additively increased this response. Taken together, these results suggest that the EC–MC interaction potentiates BMP9 signaling both in ECs and MCs and plays a critical role in the maintenance of proper vessel functions.

SGK1 is a signalling hub that controls protein synthesis and proliferation in endothelial cells

“…This effect must be related to the role of BMP9 as a maturation cytokine for endothelial cells during angiogenesis. It is important to stress that, as a maturating factor, BMP9 must be able to promote the different phases of maturation of endothelial cells during angiogenesis, that is to trigger the formation of new junctions between endothelial cells (by increasing contact protein levels), to increment new extracellular matrix secretion, to maintain a correct metabolic prolife of the new stalk cell, and to attract mural cells to consolidate the new vessel [18,33]. Protein synthesis is required for all these processes, highlighting the importance of this signalling axis in angiogenesis.…”

MicroRNA26 attenuates vascular smooth muscle maturation via endothelial BMP signalling

“…Endothelial and mural cells signal through several paracrine pathways to stabilize vessels [62,63]. BMP signalling in endothelial cells activates an axis of BMP/ Notch3/ Pdgf signalling to promote the expression of contractile vSMCs genes such as Acta2 and Myh11a in in vitro co-culture systems [64]. Specifically, BMP9 signalling via endothelial cells induces NOTCH3 in vSMCs, which in turn induces expression of Pdgfrβ and maintains the proper response to Pdgf ligands [17,65].…”

Cell Fate Determination of Lymphatic Endothelial Cells

“…TMEM100 is identified as a downstream target of the BMP9/10-ACVRL1 pathway by my and other groups [65][66][67]. Expression of TMEM100 is highly induced by BMP9 treatment in the human umbilical artery and vein endothelial cells [66,68]; it is reduced in Acvrl1-deficient embryos and adults [65][66][67]. Tmem100 −/− embryos die between E10.5 and E11.5 with severe cardiovascular defects due to downregulated NOTCH and AKT signaling [65][66][67].…”