Biglycan and decorin differentially regulate signaling in the fetal membranes

• Published in: Matrix biology Vol. 35; pp. 266 - 275
• Main Authors: Wu, Zhiping, Horgan, Casie E., Carr, Olivia, Owens, Rick T., Iozzo, Renato V., Lechner, Beatrice E.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-04-2014
• Subjects: Analysis of Variance; Animals; Biglycan - genetics; Biglycan - metabolism; Blotting, Western; Cell Culture Techniques; Decorin - genetics; Decorin - metabolism; Disease Models, Animal; DNA Primers - genetics; Ehlers-Danlos Syndrome - genetics; Enzyme-Linked Immunosorbent Assay; Extraembryonic Membranes - metabolism; Extraembryonic Membranes - physiology; Fetal membranes; Immunohistochemistry; Mice; MMP; Premature Birth - genetics; Premature Birth - metabolism; Signal Transduction - physiology; Smad; Small leucine-rich proteoglycan; TGF-β; TIMP; Transforming Growth Factor beta - metabolism; Small leucine-rich proteoglycan; SLRP; MMP; EDS; Bgn; TGFβ; Fetal membranes; TGF-β; Smad; PPROM; Dcn; TIMP
• ISSN: 0945-053X; 1569-1802
• DOI: 10.1016/j.matbio.2013.12.006

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.
•We studied fetal membranes in a biglycan/decorin null mouse model of prematurity.•Biglycan and decorin support fetal membrane remodeling in early gestation.•In late gestation, biglycan and decorin signaling promotes membrane stabilization.•TGFβ levels are affected in a gestational age and proteoglycan dependent manner.•We provide evidence for biglycan and decorin’s role in fetal membrane homeostasis.