Biglycan and decorin differentially regulate signaling in the fetal membranes.

Abstract

Preterm birth is the leading cause of newborn mortality in the United States and about one third of cases are caused by preterm premature rupture of fetal membranes, a complication that is frequently observed in patients with Ehlers-Danlos Syndrome. Notably, a subtype of Ehlers-Danlos Syndrome is caused by expression of abnormal biglycan and decorin proteoglycans. As compound deficiency of these two small leucine-rich proteoglycans is a model of preterm birth, we investigated the fetal membranes of Bgn(-/-); Dcn(-/-) double-null and single-null mice. Our results showed that biglycan signaling supported fetal membrane remodeling during early gestation in the absence of concomitant changes in TGFβ levels. In late gestation, biglycan signaling acted in a TGFβ-dependent manner to aid in membrane stabilization. In contrast, decorin signaling supported fetal membrane remodeling at early stages of gestation in a TGFβ-dependent manner, and fetal membrane stabilization at later stages of gestation without changes in TGFβ levels. Furthermore, exogenous soluble decorin was capable of rescuing the TGFβ signaling pathway in fetal membrane mesenchymal cells. Collectively, these findings provide novel targets for manipulation of fetal membrane extracellular matrix stability and could represent novel targets for research on preventive strategies for preterm premature rupture of fetal membranes.

• Authors: Zhiping Wu, Casie E Horgan, Olivia Carr, Rick T Owens, Renato V Iozzo, Beatrice E Lechner
• Journal: Matrix biology : journal of the International Society for Matrix Biology (Matrix Biol) Vol. 35 Pg. 266-75 (Apr 2014) ISSN: 1569-1802 [Electronic] Netherlands
• PMID: 24373743 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2013 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Bgn protein, mouse
• Biglycan
• DNA Primers
• Dcn protein, mouse
• Decorin
• Transforming Growth Factor beta

Topics

• Analysis of Variance
• Animals
• Biglycan (genetics, metabolism)
• Blotting, Western
• Cell Culture Techniques
• DNA Primers (genetics)
• Decorin (genetics, metabolism)
• Disease Models, Animal
• Ehlers-Danlos Syndrome (genetics)
• Enzyme-Linked Immunosorbent Assay
• Extraembryonic Membranes (metabolism, physiology)
• Immunohistochemistry
• Mice
• Premature Birth (genetics, metabolism)
• Signal Transduction (physiology)
• Transforming Growth Factor beta (metabolism)