权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Glycocalyx Syndecan-1 in Trophoblast Lipid Transport

滋养层脂质运输中的 Glycocalyx Syndecan-1

基本信息

批准号：
9039780
负责人：
Carl A Hubel
金额：
$ 9.4万
依托单位：
MAGEE-WOMEN'S RES INST AND FOUNDATION
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9039780
关键词：
Acid Lipase Apical Bathing Binding Blood Blood Circulation Blood capillaries Cell Line Cell membrane Cell surface Cells Charge Cholesterol Chorionic villi Chylomicrons Clinical Communication Competitive Binding Coupled Data Development Endocytosis Energy-Generating Resources Enzymes Epithelial Familial Hypercholesterolemia Fetal Development Fetal Growth Fetus Fibroblasts Functional disorder Future Gases Giant Cells Glycerol Glycocalyx Glycoproteins Growth Health Hep3B Heparan Sulfate Proteoglycan Heparin Heparin Lyase Heparitin Sulfate Hepatic Hepatocyte Human Hydrolysis Infant Investigation LDL-Receptor Related Protein 1 Ligand Binding Ligands Lipase Lipids Lipoprotein Binding Lipoprotein Receptor Lipoproteins Low Density Lipoprotein Receptor Measures Mediating Membrane Mesenchymal Molecular Profiling Mothers Nonesterified Fatty Acids Nutrient Organ Pathway interactions Patients Placenta Plasma Play Pre-Eclampsia Pregnancy Primary carcinoma of the liver cells Proteins Proteoglycan Research Research Project Grants Risk Role SR-B proteins Series Side Signal Transduction Small for Gestational Age Infant Source Surface Syncytiotrophoblast System Testing Tissues Triglycerides VLDL receptor Very low density lipoprotein Villous Villus Woman Work capillary cellular microvillus design fetal fetal blood lipid transport lipoprotein triglyceride member normotensive overexpression particle prenatal public health relevance receptor research study sulfation syndecan tool trophoblast uptake very low density lipoprotein triglyceride

项目摘要

DESCRIPTION (provided by applicant): The syncytiotrophoblast (STB) has critical functions including transport of gases and nutrients to the fetus. Maternal very low-density lipoproteins (VLDL) provide a significant source of free fatty acids (FFA), important for fetal growth and development. VLDL triglycerides are hydrolyzed to FFA by lipases expressed on the STB microvillous membrane (MVM), with FFA transferred to the fetus. Alternatively, however, maternal lipoproteins interact with receptors on the STB MVM, with endocytosis and intracellular hydrolysis. However, relatively little is known about the function of lipoprotein receptors on the trophoblast microvillous membrane, especially with regard to VLDL transport. Disruption of the overall system of placental lipid transfer can have a negative impact on the development of the fetus. The cell surface heparan sulfate proteoglycan (HSPG), syndecan-1 (SDC-1) functions as a receptor for various macromolecular cargo. On microvilli of hepatocytes, SDC-1 mediates cellular internalization of VLDL and remnant lipoproteins. Our preliminary data suggest that trophoblasts likewise bind and internalize VLDL by an HSPG-dependent mechanism, and that trophoblast expression of SDC-1 is significantly reduced in preeclamptic pregnancies. The hypothesis of this R03 proposal is that trophoblasts bind and internalize VLDL by an HSPG-dependent mechanism, and SDC-1 is the primary HSPG effecting this uptake. This will be tested using cells in culture, primarily 1) the human HTR-8/SVneo trophoblast cell line (HTR-8); 2) human Hep3B hepatocarcinoma cells as a positive control for SDC-1 -mediated VLDL uptake; and 3) a line of human fibroblasts (GM00701) that do not express the low-density lipoprotein (LDL) receptor and do not express SDC-1, but express high levels of functional LRP1 (multifunctional member of the LDL receptor superfamily). Aim 1, which builds upon our preliminary data, is to ascertain the role of trophoblast cell surface HSPGs in VLDL binding/uptake. Aim 2 is to determine whether the HSPG-dependent VLDL binding/uptake is primarily accomplished by SDC-1. Aim 3 is to rule out involvement of LRP1 in trophoblast internalization of VLDL. Aim 4 is to measure VLDL binding/uptake by placental villi in explant culture, comparing villi from women with preeclampsia versus uncomplicated pregnancy. The proposed work will further our understanding of lipoprotein handling by STB, and HSPG function in this regard. The research has important clinical implications given the vital importance of placental nutrient transport.