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ADAMTS9-Mediated Extracellular Matrix Dynamics Regulates Umbilical Cord Vascular Smooth Muscle Differentiation and Rotation.

Abstract：

:Despite the significance for fetal nourishment in mammals, mechanisms of umbilical cord vascular growth remain poorly understood. Here, the secreted metalloprotease ADAMTS9 is shown to be necessary for murine umbilical cord vascular development. Restricting it to the cell surface using a gene trap allele, Adamts9(Gt), impaired umbilical vessel elongation and radial growth via reduced versican proteolysis and accumulation of extracellular matrix (ECM). Both Adamts9(Gt) and conditional Adamts9 deletion revealed that ADAMTS9 produced by mesenchymal cells acted non-autonomously to regulate smooth muscle cell (SMC) proliferation, differentiation, and orthogonal reorientation during growth of the umbilical vasculature. In Adamts9(Gt/Gt), we observed interference with PDGFRβ signaling via the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway, which regulates cytoskeletal dynamics during SMC rotation. In addition, we observed disrupted Shh signaling and perturbed orientation of the mesenchymal primary cilium. Thus, ECM dynamics is a major influence on umbilical vascular SMC fate, with ADAMTS9 acting as its principal mediator.

journal_name

Cell Rep

journal_title

Cell reports

authors

Nandadasa S,Nelson CM,Apte SS

doi

10.1016/j.celrep.2015.05.005

subject

Has Abstract

pub_date

2015-06-16 00:00:00

pages

1519-28

issue

10

issn

2211-1247

pii

S2211-1247(15)00503-3

journal_volume

11

pub_type

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