Expression of Pleiotrophin and its Receptors in Human Placenta Suggests Roles in Trophoblast Life Cycle and Angiogenesis

Ball, Melanie; Carmody, Mark; Wynne, Freda; Dockery, Peter; Aigner, Achim; Cameron, Iain; Higgins, John R.; Smith, Samantha D.; Aplin, John D.; Moore, Tom

doi:10.1016/j.placenta.2009.05.001

Cited by 31 publications

(31 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, it is possible that at least some PSGs could remain bound to the cells that secrete them. Other cells such as fetal macrophages, villous mesenchyme, and core fetal vessels also express syndecan-1 (48). Syndecan-2 expression is intense in the villous stroma, and syndecans-2 and -4 are expressed mainly in the villous cytotrophoblast and extravillous cytotrophoblastic cells at early pregnancy stages.…”

Section: Discussionmentioning

confidence: 99%

“…Syndecan-2 expression is intense in the villous stroma, and syndecans-2 and -4 are expressed mainly in the villous cytotrophoblast and extravillous cytotrophoblastic cells at early pregnancy stages. Syndecan-3 staining has been reported in extravillous trophoblasts (48). A possible role for syndecans in the remodeling of extracellular matrix during the development of the villous tree was suggested after their expression was found to be altered in invasive mole and choriocarcinoma (49), but further studies are required to define their function(s) in the placenta.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Pregnancy-specific Glycoprotein 1 Induces Endothelial Tubulogenesis through Interaction with Cell Surface Proteoglycans

Lisboa

Warren

Sulkowski

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Pregnancy-specific ␤1 glycoproteins (PSGs) are the most abundant fetal proteins in the maternal bloodstream in late pregnancy. They are secreted by the syncytiotrophoblast and are detected around day 14 postfertilization. There are 11 human PSG genes, which encode a family of proteins exhibiting significant conservation at the amino acid level. We and others have proposed that PSGs have an immune modulatory function. In addition, we recently postulated that they are proangiogenic due to their ability to induce the secretion of VEGF-A and the formation of tubes by endothelial cells. The cellular receptor(s) for human PSGs remain unknown. Therefore, we conducted these studies to identify the receptor for PSG1, the highest expressed member of the family. We show that removal of cell surface glycosaminoglycans (GAGs) by enzymatic or chemical treatment of cells or competition with heparin completely inhibited binding of PSG1. In addition, PSG1 did not bind to cells lacking heparan or chondroitin sulfate on their surface, and binding was restored upon transfection with all four syndecans and glypican-1. Importantly, the presence of GAGs on the surface of endothelial cells was required for the ability of PSG1 to induce tube formation. This finding indicates that the PSG1-GAG interaction mediates at least some of the PSG1 proposed functions.Pregnancy success requires that the maternal immune system does not attack the fetal trophoblast cells, which are in direct contact with maternal blood and express genes derived from both the mother and the father. In addition, during pregnancy major vascular adaptations are required to guarantee fetal growth and survival. These include uterine vessel dilation, remodeling of the maternal decidual arteries, and angiogenesis within the placenta villi, as reviewed in Ref.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pregnancy-specific Glycoprotein 1 Induces Endothelial Tubulogenesis through Interaction with Cell Surface Proteoglycans

Lisboa

Warren

Sulkowski

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Interestingly, the expression of both syndecan proteins was diminished in placentas from patients suffering from pre-eclampsia as compared to placentas from patients with normally developing pregnancies (Figure 6). The presence of pleiotrophin specifically in human placenta has been reported earlier [35]. …”

Section: Resultsmentioning

confidence: 56%

“…Of note, syndecan-1 expression was already previously suggested as a risk factor for pre-eclampsia [45]. Pleiotrophin and syndecans might regulate trophoblast life cycle and angiogenesis, and intriguingly, the trophoblast expression of pleiotrophin occurs only in human and higher primates [32,35]. Signaling of the primate-specific Y-P30 peptide might be involved in these processes.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Y-P30/Dermcidin expression and properties of the Y-P30 peptide

et al. 2014

View full text Add to dashboard Cite

BackgroundThe survival promoting peptide Y-P30 has a variety of neuritogenic and neuroprotective effects in vitro and in vivo. In previous work we reported the expression of Y-P30/dermcidin in maternal peripheral blood mononuclear cells (PBMCs) and the transport of the protein to the fetal brain. In this study we analyzed hormonal regulation of Y-P30 in human immune cells and expression of Y-P30 in the placenta. We further studied the stability and secretion of the Y-P30 peptide.ResultsWe found indications that Y-P30 might be produced in human placenta. The Y-P30 mRNA was rarely found in isolated human PBMCs and alpha-feto-protein, human chorionic gonadotropin as well as estradiol combined with progesterone could not induce Y-P30 expression. Y-P30 was found to be extraordinarily stable; therefore, contamination with the peptide and the Y-P30/Dermcidin precursor mRNA is a serious concern in experiments looking at the expression of Y-P30/Dermcidin. In cultured cell lines and primary neurons we found that Y-P30 could be released, but neuronal uptake of Y-P30 was not observed.ConclusionsOur data suggest that a source of Y-P30 apart from eccrine glands might be the placenta. The peptide can be secreted together with the signaling peptide and it might reach the fetal brain where it can exert its neuritogenic functions by binding to neuronal membranes.

show abstract

“…Overexpression of PTN abrogated miR‐384 induced cell growth and invasion inhibition. As an oncogene, PTN is overexpressed in a number of human cancers, and its overexpression contributes to malignant transformation by regulating the expression of a number of genes that participate in multiple aspects of tumorigenesis, such as angiogenesis, cell cycle progression, cell invasion, migration, metastasis and angiogenesis . PTN is also a strong mitogen of hepatocytes and is involved in liver regeneration .…”

Section: Discussionmentioning

confidence: 99%

Pleiotrophin, a target of miR‐384, promotes proliferation, metastasis and lipogenesis in HBV‐related hepatocellular carcinoma

Bai

Xia

Sun

et al. 2017

J Cellular Molecular Medi

View full text Add to dashboard Cite

Hepatitis B virus (HBV) infection plays a crucial role and is a major cause of hepatocellular carcinoma (HCC) in China. microRNAs (miRNAs) have emerged as key players in hepatic steatosis and carcinogenesis. We found that down‐regulation of miR‐384 expression was a common event in HCC, especially HBV‐related HCC. However, the possible function of miR‐384 in HBV‐related HCC remains unclear. The oncogene pleiotrophin (PTN) was a target of miR‐384. HBx inhibited miR‐384, increasing PTN expression. The PTN receptor N‐syndecan was highly expressed in HCC. PTN induced by HBx acted as a growth factor via N‐syndecan on hepatocytes and further promoted cell proliferation, metastasis and lipogenesis. PTN up‐regulated sterol regulatory element‐binding protein 1c (SREBP‐1c) through the N‐syndecan/PI3K/Akt/mTORC1 pathway and the expression of lipogenic genes, including fatty acid synthesis (FAS). PTN‐mediated de novo lipid synthesis played an important role in HCC proliferation and metastasis. PI3K/AKT and an mTORC1 inhibitor diminished PTN‐induced proliferation, metastasis and lipogenesis. Taken together, these data strongly suggest that the dysregulation of miR‐384 could play a crucial role in HBV related to HCC, and the target gene of miR‐384, PTN, represents a new potential therapeutic target for the prevention of hepatic steatosis and further progression to HCC after chronic HBV infection.

show abstract

Expression of Pleiotrophin and its Receptors in Human Placenta Suggests Roles in Trophoblast Life Cycle and Angiogenesis

Cited by 31 publications

References 25 publications

Pregnancy-specific Glycoprotein 1 Induces Endothelial Tubulogenesis through Interaction with Cell Surface Proteoglycans

Pregnancy-specific Glycoprotein 1 Induces Endothelial Tubulogenesis through Interaction with Cell Surface Proteoglycans

Analysis of Y-P30/Dermcidin expression and properties of the Y-P30 peptide

Pleiotrophin, a target of miR‐384, promotes proliferation, metastasis and lipogenesis in HBV‐related hepatocellular carcinoma

Contact Info

Product

Resources

About