| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Department of Obstetrics and Gynecology, Faculty of Medicine (T.N., T.F., M.K., T.Y., Y.O., M.M., S.K., Y.T.), University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan 113-8655; and Department of Obstetrics and Gynecology, Xiehe Hospital, Tongii Faculty of Medicine (L.Z.), Huazhong University of Science and Technology, Jiefang Dadao, Hubei, Wuhan 430000, China
Address all correspondence and requests for reprints to: Tomoyuki Fujii, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail: fujiit-tky{at}umin.ac.jp.
Sufficient cytotrophoblast (CT) invasion into the uterine wall and subsequent remodeling of maternal uterine vasculature is critical to establish uteroplacental circulation. The production of vascular endothelial growth factor (VEGF) family molecules is confirmed in placental cells including CTs, but it is not elucidated how the VEGF system in CTs is controlled by oxygen tension and how it is involved in the development of placental circulation. To address this, we explored the effect of oxygen tension on the expression of VEGF, placenta growth factor (PlGF), and their antagonist, soluble fms-like tyrosine kinase-1 (sFlt-1) using ELISA and real-time PCR in a primary CT cell culture. For comparison, the same was conducted in parallel using other cells comprising placenta, such as human umbilical vein endothelial cells (HUVECs) and villous fibroblasts (VFs). Reduced oxygen resulted in a pronounced increase in sFlt-1 mRNA amount and sFlt-1 release into the culture media in CTs, whereas this was not the case with HUVECs and VFs. Free (not bound to sFlt-1) VEGF was not detected in CT culture media regardless of oxygen concentration, even though VEGF expression was stimulated by reduced oxygen in CTs, which was similar to the stimulation in HUVECs and VFs. Free PlGF was also diminished in CT culture media by reduced oxygen. These results implicate that CTs possess a unique property to enhance sFlt-1 production under reduced oxygen, which could consequently antagonize angiogenic activity of VEGF and PlGF. The presented findings might provide a framework with which to understand the mechanism of uterine vascular remodeling and its perturbations as exemplified in preeclampsia.
This article has been cited by other articles:
 |
|
 |
|
  L. Martorell, M. Gentile, J. Rius, C. Rodriguez, J. Crespo, L. Badimon, and J. Martinez-Gonzalez The Hypoxia-Inducible Factor 1/NOR-1 Axis Regulates the Survival Response of Endothelial Cells to Hypoxia Mol. Cell. Biol., November 1, 2009; 29(21): 5828 - 5842. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Bruegmann, R. Gruemmer, J. Neulen, and K. Motejlek Regulation of soluble vascular endothelial growth factor receptor 1 secretion from human endothelial cells by tissue inhibitor of metalloproteinase 1 Mol. Hum. Reprod., November 1, 2009; 15(11): 749 - 756. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. P. Thomas, J. I. Andrews, N. S. Raikwar, E. A. Kelley, F. Herse, R. Dechend, T. G. Golos, and K. Z. Liu A Recently Evolved Novel Trophoblast-Enriched Secreted Form of fms-Like Tyrosine Kinase-1 Variant Is Up-Regulated in Hypoxia and Preeclampsia J. Clin. Endocrinol. Metab., July 1, 2009; 94(7): 2524 - 2530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Wang, S. Rana, and S. A. Karumanchi Preeclampsia: The Role of Angiogenic Factors in Its Pathogenesis Physiology, June 1, 2009; 24(3): 147 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Muehlenbachs, M. Fried, J. Lachowitzer, T. K. Mutabingwa, and P. E. Duffy From the Cover: Natural selection of FLT1 alleles and their association with malaria resistance in utero PNAS, September 23, 2008; 105(38): 14488 - 14491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Munaut, S. Lorquet, C. Pequeux, S. Blacher, S. Berndt, F. Frankenne, and J.-M. Foidart Hypoxia is responsible for soluble vascular endothelial growth factor receptor-1 (VEGFR-1) but not for soluble endoglin induction in villous trophoblast Hum. Reprod., June 1, 2008; 23(6): 1407 - 1415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Zhou, S. Ahmad, T. Mi, S. Abbasi, L. Xia, M.-C. Day, S. M. Ramin, A. Ahmed, R. E. Kellems, and Y. Xia Autoantibody From Women With Preeclampsia Induces Soluble Fms-Like Tyrosine Kinase-1 Production via Angiotensin Type 1 Receptor and Calcineurin/Nuclear Factor of Activated T-Cells Signaling Hypertension, April 1, 2008; 51(4): 1010 - 1019. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. P. Thomas, J. I. Andrews, and K. Z. Liu Intronic polyadenylation signal sequences and alternate splicing generate human soluble Flt1 variants and regulate the abundance of soluble Flt1 in the placenta FASEB J, December 1, 2007; 21(14): 3885 - 3895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Xia, C. C. Zhou, S. M. Ramin, and R. E. Kellems Angiotensin Receptors, Autoimmunity, and Preeclampsia J. Immunol., September 15, 2007; 179(6): 3391 - 3395. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. C. R. Prickett, C. W. H. Rumball, A. J. Buckley, F. H. Bloomfield, T. G. Yandle, J. E. Harding, and E. A. Espiner C-Type Natriuretic Peptide Forms in the Ovine Fetal and Maternal Circulations: Evidence for Independent Regulation and Reciprocal Response to Undernutrition Endocrinology, August 1, 2007; 148(8): 4015 - 4022. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xia, S. M. Ramin, and R. E. Kellems Potential Roles of Angiotensin Receptor-Activating Autoantibody in the Pathophysiology of Preeclampsia Hypertension, August 1, 2007; 50(2): 269 - 275. [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Lockwood, P. Toti, F. Arcuri, E. Norwitz, E. F. Funai, S.-T. J. Huang, L. F. Buchwalder, G. Krikun, and F. Schatz Thrombin Regulates Soluble fms-Like Tyrosine Kinase-1 (sFlt-1) Expression in First Trimester Decidua: Implications for Preeclampsia Am. J. Pathol., April 1, 2007; 170(4): 1398 - 1405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Zhou, S. Ahmad, T. Mi, L. Xia, S. Abbasi, P. W. Hewett, C. Sun, A. Ahmed, R. E. Kellems, and Y. Xia Angiotensin II Induces Soluble fms-Like Tyrosine Kinase-1 Release via Calcineurin Signaling Pathway in Pregnancy Circ. Res., January 5, 2007; 100(1): 88 - 95. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Nevo, N. Soleymanlou, Y. Wu, J. Xu, J. Kingdom, A. Many, S. Zamudio, and I. Caniggia Increased expression of sFlt-1 in in vivo and in vitro models of human placental hypoxia is mediated by HIF-1 Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2006; 291(4): R1085 - R1093. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Hoffmann, J.-J. Feige, and N. Alfaidy Expression and Oxygen Regulation of Endocrine Gland-Derived Vascular Endothelial Growth Factor/Prokineticin-1 and Its Receptors in Human Placenta during Early Pregnancy Endocrinology, April 1, 2006; 147(4): 1675 - 1684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Armant, B. A. Kilburn, A. Petkova, S. S. Edwin, Z. M. Duniec-Dmuchowski, H. J. Edwards, R. Romero, and R. E. Leach Human trophoblast survival at low oxygen concentrations requires metalloproteinase-mediated shedding of heparin-binding EGF-like growth factor Development, February 15, 2006; 133(4): 751 - 759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Shibata, A. Rajakumar, R. W. Powers, R. W. Larkin, C. Gilmour, L. M. Bodnar, W. R. Crombleholme, R. B. Ness, J. M. Roberts, and C. A. Hubel Soluble fms-Like Tyrosine Kinase 1 Is Increased in Preeclampsia But Not in Normotensive Pregnancies with Small-for-Gestational-Age Neonates: Relationship to Circulating Placental Growth Factor J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4895 - 4903. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
