Anticoagulant dermatan sulfate proteoglycan (decorin) in the term human placenta.
Normal pregnancy is characterized by increased in vivo thrombin generation. A greater proportion of endogenously generated thrombin is complexed to heparin cofactor II in plasma from pregnant women compared to plasma from nonpregnant ones. The increase in thrombin-heparin cofactor II complexes suggests that the site of the additional thrombin generation is relatively rich in dermatan sulfate. We postulated that the site of thrombin generation may be the placenta since endogenous thrombin generation returns rapidly to normal after delivery. This report describes the isolation and characterization of placental dermatan sulfate proteoglycan from villous tissue of the term human placenta. Placental dermatan sulfate was isolated by guanidine HCI extraction and anion exchange chromatography. The isolated material was found to have anticoagulant activity with a relative activity of approximately 40% of that of a porcine mucosal dermatan sulfate which is undergoing clinical trial as an antithrombotic agent. The dermatan sulfate was present as a proteoglycan with a molecular mass of 90-150 kD. Upon degradation with chondroitin ABC lyase, the core protein was demonstrated to be a doublet with molecular masses of 42 and 44 kD. This core protein reacted with antiserum against the core protein of decorin on Western analysis. The role of this placental dermatan sulfate in local regulation of thrombin in the placenta warrants further study.
The Department of Medicine, University of Western Ontario, London, Canada. mdelorme@julian.uwo.ca
M A
MA
Delorme
L
L
Xu
L
L
Berry
L
L
Mitchell
M
M
Andrew
D000423:Alcian Blue; D000925:Anticoagulants / Q000032:analysis*; D011508:Chondroitin Sulfate Proteoglycans / Q000032:analysis* / Q000737:chemistry; D002824:Chorionic Villi / Q000378:metabolism; D004396:Coloring Agents; D058575:Decorin; D003871:Dermatan Sulfate / Q000032:analysis* / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins; D005260:Female; D006801:Humans; D007743:Labor, Obstetric; D008970:Molecular Weight; D010920:Placenta / Q000737:chemistry*; D011247:Pregnancy; D011509:Proteoglycans / Q000032:analysis*; D012967:Sodium Dodecyl Sulfate; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors
D000925:Anticoagulants; D011508:Chondroitin Sulfate Proteoglycans; D004396:Coloring Agents; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; C032649:dermatan sulfate proteoglycan; D003871:Dermatan Sulfate; D012967:Sodium Dodecyl Sulfate; D000423:Alcian Blue