Review: The enigmatic role of endoglin in the placenta

Gregory, Allison; Xu, Guo; Sotov, Valentin; Letarte, Michelle

doi:10.1016/j.placenta.2013.10.020

Cited by 96 publications

(83 citation statements)

References 45 publications

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“…In a second step, we analyzed whether CTB and STB exhibit physiological features similar to in vivo conditions [31,32,33]. Therefore, we compared the gene expression and secretion of human chorionic gonadotropin ( hCG ), human placental lactogen ( hPL ), and endoglin between CTB and STB.…”

Section: Resultsmentioning

confidence: 99%

Novel Insights into Concepts and Directionality of Maternal–Fetal Cholesterol Transfer across the Human Placenta

Kallol

Huang

Müller

et al. 2018

IJMS

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Cholesterol is indispensable for cellular membrane composition and function. It is also a precursor for the synthesis of steroid hormones, which promote, among others, the maturation of fetal organs. A role of the ATP-binding-cassette-transporter-A1 (ABCA1) in the transport of maternal cholesterol to the fetus was suggested by transferring cholesterol to apolipoprotein-A-1 (apo-A1), but the directionality of the apoA-1/ABCA1-dependent cholesterol transport remains unclear. We isolated primary trophoblasts from term placentae to test the hypotheses that (1) apoA-1/ABCA1 dispatches cholesterol mainly towards the fetus to support fetal developmental maturation at term, and (2) differentiated syncytiotrophoblasts (STB) exert higher cholesterol transport activity than undifferentiated cytotrophoblasts (CTB). As experimental models, we used (1) trophoblast monolayers grown on Transwell® system consisting of apical (maternal-like) and basal (fetal-like) compartments, and (2) trophoblasts grown on conventional culture plates at CTB and STB stages. Surprisingly, apoA-1-mediated cholesterol efflux operated almost exclusively at the apical-maternal side, where ABCA1 was also localized by immunofluorescence. We found greater cholesterol efflux capacity in STB, which was increased by liver-X-receptor agonist treatment and decreased by ABCA1 inhibition. We conclude that at term the apoA-1/ABCA1 pathway is rather involved in cholesterol transport to the mother than in transfer to the fully developed fetus.

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Section: Resultsmentioning

confidence: 99%

Novel Insights into Concepts and Directionality of Maternal–Fetal Cholesterol Transfer across the Human Placenta

Kallol

Huang

Müller

et al. 2018

IJMS

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“…Endoglin-Fc binds to BMP9 and BMP10 tightly, competing for the type II receptor binding and inhibiting BMP9 and BMP10 signalling [5]. Soluble endoglin, without the Fc fusion and at large molar excess, was also shown to inhibit BMP9-induced Smad1/5 phosphorylation in mouse embryonic ECs [49]. Very recently, it was shown that TGFβ family ligands could function as antagonists by competing with the type II receptors and activin A has been shown to antagonize BMP9 and BMP10 signalling in vitro [50].…”

Section: Extracellular Bmp Antagonistsmentioning

confidence: 99%

Regulation of the ALK1 ligands, BMP9 and BMP10

Salmon

Jiang

et al. 2016

Biochemical Society Transactions

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Bone morphogenetic protein (BMP)9 and BMP10 are high affinity ligands for activin receptor-like kinase 1 (ALK1), a type I BMP receptor mainly expressed on vascular endothelial cells (ECs). ALK1-mediated BMP9/BMP10 signalling pathways have emerged as essential in EC biology and in angiogenesis. Several genetic mutations in the genes encoding the ligands and receptors of this pathway have been reported in two cardiovascular diseases, pulmonary arterial hypertension (PAH) and hereditary haemorrhagic telangiectasia (HHT). Administration of recombinant BMP9 reverses experimental PAH in preclinical rodent models. Dalantercept, an Fc-fusion protein of the extracellular domain of ALK1 and a ligand trap for BMP9 and BMP10, is in phase II clinical trials for anti-tumour angiogenesis. Understanding the regulation of BMP9 and BMP10, at both gene and protein levels, under physiological and pathological conditions, will reveal essential information and potential novel prognostic markers for the BMP9/BMP10-targeted therapies.

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“…However, this interaction has not been demonstrated clearly. It has been reported that Sol-Eng cannot directly scavenge TGF-β unless a complex of Sol-Eng-sTβRII is present [60,61] and that the ability of a recombinant Sol-Eng to block TGF-β1 and thus block its binding to cell surface receptors was very low compared with soluble TβRII [62]. Consequently, our hypothesis is that the high levels of Sol-Eng present in the serum of S-ENG + mice do not interfere with the TGF-β pathway and the reduced fibrosis and inflammation after ureteral ligation observed in S-ENG + mice is not due to the scavenging of TGF-β by Sol-Eng.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Overexpression of the short endoglin isoform reduces renal fibrosis and inflammation after unilateral ureteral obstruction

Muñoz‐Félix

Pérez-Roque

Núñez-Gómez

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Transforming growth factor beta 1 (TGF-β1) is one of the most studied cytokines involved in renal tubulo-interstitial fibrosis, which is characterized by myofibroblast abundance and proliferation, and high buildup of extracellular matrix in the tubular interstitium leading to organ failure. Endoglin (Eng) is a 180-kDa homodimeric transmembrane protein that regulates a great number of TGF-β1 actions in different biological processes, including ECM synthesis. High levels of Eng have been observed in experimental models of renal fibrosis or in biopsies from patients with chronic kidney disease. In humans and mice, two Eng isoforms are generated by alternative splicing, L-Eng and S-Eng that differ in the length and composition of their cytoplasmic domains. We have previously described that L-Eng overexpression promotes renal fibrosis after unilateral ureteral obstruction (UUO). However, the role of S-Eng in renal fibrosis is unknown and its study would let us analyze the possible function of the cytoplasmic domain of Eng in this process. For this purpose, we have generated a mice strain that overexpresses S-Eng (S-ENG(+)) and we have performed an UUO in S-ENG(+) and their wild type (WT) control mice. Our results indicate that obstructed kidney of S-ENG(+) mice shows lower levels of tubulo-interstitial fibrosis, less inflammation and less interstitial cell proliferation than WT littermates. Moreover, S-ENG(+) mice show less activation of Smad1 and Smad2/3 pathways. Thus, S-Eng overexpression reduces UUO-induced renal fibrosis and some associated mechanisms. As L-Eng overexpression provokes renal fibrosis we conclude that Eng-mediated induction of renal fibrosis in this model is dependent on its cytoplasmic domain.

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Review: The enigmatic role of endoglin in the placenta

Cited by 96 publications

References 45 publications

Novel Insights into Concepts and Directionality of Maternal–Fetal Cholesterol Transfer across the Human Placenta

Novel Insights into Concepts and Directionality of Maternal–Fetal Cholesterol Transfer across the Human Placenta

Regulation of the ALK1 ligands, BMP9 and BMP10

Overexpression of the short endoglin isoform reduces renal fibrosis and inflammation after unilateral ureteral obstruction

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