Stimulation of DNA synthesis in trophoblasts and human umbilical vein endothelial cells by hepatocyte growth factor bound to extracellular matrix.
Hepatocyte growth factor (HGF) promotes the growth not only of hepatocytes but also of several other types of cells such as cytotrophoblasts and endothelial cells. Recent studies have revealed that HGF is trapped in the extracellular (ECM) matrix through heparan sulphate in vivo, thereby acting as a mitogen for hepatocytes in cooperation with heparan sulphate. In this study, we detected HGF protein in chorionic tissue and placental tissue extracts, and found that HGF and heparan sulphate were co-distributed in the endothelial basement membrane and trophoblast basement membrane on immunohistochemical examination. The rates of DNA synthesis in primary cultured cytotrophoblasts and human umbilical vein endothelial cells (HUVEC) cultured on HGF-bound Matrigeltrade mark were 6-8 times those of control cytotrophoblasts and HUVEC. When Matrigeltrade mark dishes were pretreated with heparinase and heparitinase prior to binding of HGF, stimulation of DNA synthesis was markedly decreased. A considerable decrease in stimulation of DNA synthesis was observed following washing of HGF-bound Matrigeltrade mark with 1 m acetic acid, 1 m NaCl and 0.1 per cent trypsin, but not following treatment with chondroitinase ABC. These observations suggest that HGF can be trapped in ECM in vivo, thereby acting as a mitogen for cytotrophoblasts and placental vein endothelial cells in cooperation with heparan sulphate.
Sakakura
S
S
Department of Obstetrics and Gynecology, Tondabayashi Hospital, 36-3-1 Koyodai, Tondabayashi-shi, Osaka, 584-0082, Japan.
Saito
S
S
Morikawa
H
H
D000704:Analysis of Variance; D001672:Biocompatible Materials; D002478:Cells, Cultured; D003094:Collagen; D004247:DNA / Q000096:biosynthesis*; D004338:Drug Combinations; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D011509:Proteoglycans; D011994:Recombinant Proteins / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D001672:Biocompatible Materials; D004338:Drug Combinations; D016228:Endothelial Growth Factors; D019812:Heparan Sulfate Proteoglycans; D007797:Laminin; D008222:Lymphokines; D011509:Proteoglycans; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C059485:matrigel; D017228:Hepatocyte Growth Factor; D003094:Collagen; D004247:DNA