Heparin-binding epidermal growth factor and its receptors mediate decidualization and potentiate survival of human endometrial stromal cells.
Heparin-binding epidermal growth factor (HB-EGF) has pleiotropic biological functions in many tissues, including those of the female reproductive tract. It facilitates embryo development and mediates implantation and is thought to have a function in endometrial receptivity and maturation. The mature HB-EGF molecule manifests its activity as either a soluble factor (sol-HB-EGF) or a transmembrane precursor (tm-HB-EGF) and can bind two receptors, EGFR and ErbB4/HER4. In this study, we identify factors that modulate expression of HB-EGF, EGFR, and ErbB4 in endometrial stromal cells in vitro. We demonstrate that levels of sol- and tm-HB-EGF, EGFR, and ErbB4 are increased by cAMP, a potent inducer of decidualization of the endometrial stroma. We also show that production of sol- and tm-HB-EGF is differentially modulated by TNF alpha and TGF beta. Our data suggest that HB-EGF has a function in endometrial maturation in mediating decidualization and attenuating TNF alpha- and TGF beta-induced apoptosis of endometrial stromal cells.
Chobotova
Katya
K
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK.
Karpovich
Natalia
N
Carver
Janet
J
Manek
Sanjiv
S
Gullick
William J
WJ
Barlow
David H
DH
Mardon
Helen J
HJ
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000328:Adult; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000494:pharmacology; D003656:Decidua / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004717:Endometrium / Q000166:cytology* / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000502:physiology*; D066246:ErbB Receptors / Q000187:drug effects / Q000502:physiology*; D005260:Female; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008875:Middle Aged; D011388:Prolactin / Q000502:physiology; D066247:Receptor, ErbB-4; D017154:Stromal Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*
C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D015124:8-Bromo Cyclic Adenosine Monophosphate; D004815:Epidermal Growth Factor; D011388:Prolactin; D000242:Cyclic AMP; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4