title: 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.affiliation: Department of Pediatrics, Women and Infants Hospital of Rhode Island, The Warren Alpert Medical School of Brown University, 101 Dudley Street, Providence, RI 02905, USA.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, Women and Infants Hospital of Rhode Island, The Warren Alpert Medical School of Brown University, 101 Dudley Street, Providence, RI 02905, USA.
authors.forename: Casie E
authors.initials: CE
authors.lastname: Horgan
authors.affiliation: Department of Pediatrics, Women and Infants Hospital of Rhode Island, The Warren Alpert Medical School of Brown University, 101 Dudley Street, Providence, RI 02905, USA.
authors.forename: Olivia
authors.initials: O
authors.lastname: Carr
authors.affiliation: Lifecell Corporation, 1 Millennium Way, Branchburg, NJ 08876, USA.
authors.forename: Rick T
authors.initials: RT
authors.lastname: Owens
authors.affiliation: Department of Pathology, Anatomy & Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
authors.forename: Renato V
authors.initials: RV
authors.lastname: Iozzo
authors.affiliation: Department of Pediatrics, Women and Infants Hospital of Rhode Island, The Warren Alpert Medical School of Brown University, 101 Dudley Street, Providence, RI 02905, USA. Electronic address: blechner@wihri.org.
authors.forename: Beatrice E
authors.initials: BE
authors.lastname: Lechner
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D058578:Biglycan / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D018929:Cell Culture Techniques; D017931:DNA Primers / Q000235:genetics; D058575:Decorin / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004535:Ehlers-Danlos Syndrome / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005321:Extraembryonic Membranes / Q000378:metabolism / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D047928:Premature Birth / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C546885:Bgn protein, mouse; D058578:Biglycan; D017931:DNA Primers; C546879:Dcn protein, mouse; D058575:Decorin; D016212:Transforming Growth Factor beta
keywords: Fetal membranes; MMP; Smad; Small leucine-rich proteoglycan; TGF-β; TIMP