Regulated expression of the trophoblast alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein. Differentiation and cAMP modulate protein and mRNA levels.
The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2MR/LRP) has several ligands including activated alpha 2-macroglobulin, pregnancy zone protein, and very low density lipoproteins enriched with apolipoprotein E. The diversity of ligands suggests a role for the alpha 2MR/LRP in a variety of processes including tissue remodeling and lipoprotein metabolism. We examined alpha 2MR/LRP in placental trophoblasts, invasive cells that also function in lipid transport and cholesterol metabolism. alpha 2MR/LRP protein was localized by immunohistochemistry in the syncytiotrophoblast of term placenta. Cytotrophoblasts did not stain prominently. alpha 2MR/LRP (protein and message) in primary cultures of human trophoblast cells increased as cytotrophoblasts differentiated into syncytiotrophoblast. 8-Bromo-cAMP prevented this increase and suppressed alpha 2MR/LRP expression. The cyclic nucleotide had similar suppressive effects on alpha 2MR/LRP in BeWo choriocarcinoma cells. In contrast, low density lipoprotein receptor gene expression was increased. We conclude that: 1) there is a differentiation-dependent pattern of alpha 2MR/LRP expression in the human trophoblast; 2) cAMP negatively regulates alpha 2MR/LRP; 3) there is an inverse relationship between alpha 2MR/LRP and low density lipoprotein receptor gene expression in trophoblast cells.
Gåfvels
M E
ME
Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia 19104.
Coukos
G
G
Sayegh
R
R
Coutifaris
C
C
Strickland
D K
DK
Strauss
J F
JF
D001483:Base Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured; D002824:Chorionic Villi / Q000378:metabolism* / Q000648:ultrastructure; D000242:Cyclic AMP / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism
D026503:Low Density Lipoprotein Receptor-Related Protein-1; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D000242:Cyclic AMP