Decorin and biglycan immunolocalization in non‐villous structures of healthy and pathological human placentas

Borbely, Alexandre Urban; Daher, Sílvia; Ishigai, Marcia M.; Mattar, Rosiane; Sun, Sue Yazaki; Knöfler, Martin; Bevilacqua, Estela; Oliveira, Sérgio Ferreira de

doi:10.1111/his.12304

Cited by 15 publications

(12 citation statements)

References 33 publications

(55 reference statements)

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“…Very little information is available as to whether DCN acts as a protective molecule in trophoblastic tumorigenesis or metastasis to the placenta from pregnancy-associated cancers in maternal organs including the breast. Recently Borbely et al 148 reported immunohistochemical localization of DCN protein in trophoblast cells of invasive pregnancies including placenta acreta accreta, invasive moles and choriocarcinomas, the significance of which remains unknown. One possibility is that these hyper-invasive placental pathologies involve epithelialmesenchymal transition of the trophoblast, allowing cells to make this mesenchymal molecule.…”

Section: Gaps In Knowledge and Future Directionsmentioning

confidence: 99%

Mechanisms of trophoblast migration, endometrial angiogenesis in preeclampsia: The role of decorin

Lala

Nandi

2016

Cell Adhesion & Migration

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The objective of the present review is to synthesize the information on the cellular and molecular players responsible for maintaining a homeostatic balance between a naturally invasive human placenta and the maternal uterus in pregnancy; to review the roles of decorin (DCN) as a molecular player in this homeostasis; to list the common maladies associated with a break-down in this homeostasis, resulting from a hypo-invasive or hyper-invasive placenta, and their underlying mechanisms. We show that both the fetal components of the placenta, represented primarily by the extravillous trophoblast, and the maternal component represented primarily by the decidual tissue and the endometrial arterioles, participate actively in this balance. We discuss the process of uterine angiogenesis in the context of uterine arterial changes during normal pregnancy and preeclampsia. We compare and contrast trophoblast growth and invasion with the processes involved in tumorigenesis with special emphasis on the roles of DCN and raise important questions that remain to be addressed. Decorin (DCN) is a small leucine-rich proteoglycan produced by stromal cells, including dermal fibroblasts, chondrocytes, chorionic villus mesenchymal cells and decidual cells of the pregnant endometrium. It contains a 40 kDa protein core having 10 leucine-rich repeats covalently linked with a glycosaminoglycan chain. Biological functions of DCN include: collagen assembly, myogenesis, tissue repair and regulation of cell adhesion and migration by binding to ECM molecules or antagonising multiple tyrosine kinase receptors (TKR) including EGFR, IGF-IR, HGFR and VEGFR-2. DCN restrains angiogenesis by binding to thrombospondin-1, TGFβ, VEGFR-2 and possibly IGF-IR. DCN can halt tumor growth by antagonising oncogenic TKRs and restraining angiogenesis. DCN actions at the fetal-maternal interface include restraint of trophoblast migration, invasion and uterine angiogenesis. We demonstrate that DCN overexpression in the decidua is associated with preeclampsia (PE); this may have a causal role in PE by compromising endovascular differentiation of the trophoblast and uterine angiogenesis, resulting in poor arterial remodeling. Elevated DCN level in the maternal blood is suggested as a potential biomarker in PE.

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Section: Gaps In Knowledge and Future Directionsmentioning

confidence: 99%

Mechanisms of trophoblast migration, endometrial angiogenesis in preeclampsia: The role of decorin

Lala

Nandi

2016

Cell Adhesion & Migration

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“…Decorin, primarily synthesized by fibroblasts and myofibroblasts, is a member of the small leucine-rich proteoglycan (SLRP) family [ 17 , 18 ]. Borbely et al indicated that decorin was implicated in the invasive activity of EVT cells in pathology of both healthy and disordered placentas [ 19 ]. It has been reported that decorin might contribute to the regulation of trophoblast cells' migration and invasion potentials in the mammal placentas [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Decorin-Mediated Inhibition of Human Trophoblast Cells Proliferation, Migration, and Invasion and Promotion of ApoptosisIn Vitro

Zou

Lü

et al. 2015

BioMed Research International

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Preeclampsia (PE) is a unique complication of pregnancy, the pathogenesis of which has been generally accepted to be associated with the dysfunctions of extravillous trophoblast (EVT) including proliferation, apoptosis, and migration and invasion. Decorin (DCN) has been proved to be a decidua-derived TGF-binding proteoglycan, which negatively regulates proliferation, migration, and invasiveness of human extravillous trophoblast cells. In this study, we identified a higher expression level of decorin in severe PE placentas by both real-time reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). And an inhibitory effect of decorin on proliferation, migration, and invasion and an enhanced effect on apoptosis in trophoblast cells HTR-8/SVneo and JEG-3 were validated in vitro. Also the modulations of decorin on trophoblast cells' metastasis and invasion functions were detected through regulating the matrix metalloproteinases (MMP2 and MMP9). Thus, we suggested that the contribution of decorin to the modulation of trophoblast cells might have implications for the pathogenesis of preeclampsia.

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“…Borbely et al 23 have reported that BGN protein expression was localized to extravillous trophoblasts in the first trimester placentae of normal and of molar pregnancies, suggesting a role for BGN in the regulation of invasive properties of extravillous trophoblasts. However, the temporal relationship between reduced BGN expression and FGR is yet to be investigated.…”

mentioning

confidence: 99%

Expression of Biglycan in First Trimester Chorionic Villous Sampling Placental Samples and Altered Function in Telomerase-Immortalized Microvascular Endothelial Cells

Chui

Gunatillake

Brennecke

et al. 2017

ATVB

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Objective— Biglycan (BGN) has reduced expression in placentae from pregnancies complicated by fetal growth restriction (FGR). We used first trimester placental samples from pregnancies with later small for gestational age (SGA) infants as a surrogate for FGR. The functional consequences of reduced BGN and the downstream targets of BGN were determined. Furthermore, the expression of targets was validated in primary placental endothelial cells isolated from FGR or control pregnancies. Approach and Results— BGN expression was determined using real-time polymerase chain reaction in placental tissues collected during chorionic villous sampling performed at 10 to 12 weeks’ gestation from pregnancies that had known clinical outcomes, including SGA. Short-interference RNA reduced BGN expression in telomerase-immortalized microvascular endothelial cells, and the effect on proliferation, angiogenesis, and thrombin generation was determined. An angiogenesis array identified downstream targets of BGN, and their expression in control and FGR primary placental endothelial cells was validated using real-time polymerase chain reaction. Reduced BGN expression was observed in SGA placental tissues. BGN reduction decreased network formation of telomerase-immortalized microvascular endothelial cells but did not affect thrombin generation or cellular proliferation. The array identified target genes, which were further validated: angiopoetin 4 ( ANGPT4 ), platelet-derived growth factor receptor α ( PDGFRA ), tumor necrosis factor superfamily member 15 ( TNFSF15 ), angiogenin ( ANG ), serpin family C member 1 ( SERPIN1 ), angiopoietin 2 ( ANGPT2 ), and CXC motif chemokine 12 ( CXCL12 ) in telomerase-immortalized microvascular endothelial cells and primary placental endothelial cells obtained from control and FGR pregnancies. Conclusions— This study reports a temporal relationship between altered placental BGN expression and subsequent development of SGA. Reduction of BGN in vascular endothelial cells leads to disrupted network formation and alterations in the expression of genes involved in angiogenesis. Therefore, differential expression of these may contribute to aberrant angiogenesis in SGA pregnancies.

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Decorin and biglycan immunolocalization in non‐villous structures of healthy and pathological human placentas

Cited by 15 publications

References 33 publications

Mechanisms of trophoblast migration, endometrial angiogenesis in preeclampsia: The role of decorin

Mechanisms of trophoblast migration, endometrial angiogenesis in preeclampsia: The role of decorin

Decorin-Mediated Inhibition of Human Trophoblast Cells Proliferation, Migration, and Invasion and Promotion of ApoptosisIn Vitro

Expression of Biglycan in First Trimester Chorionic Villous Sampling Placental Samples and Altered Function in Telomerase-Immortalized Microvascular Endothelial Cells

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