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Titolo:
Hypoxia-inducible factor-1 mediates the biological effects of oxygen on human trophoblast differentiation through TGF beta(3)
Autore:
Caniggia, I; Mostachfi, H; Winter, J; Gassmann, M; Lye, SJ; Kuliszewski, M; Post, M;
Indirizzi:
Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Obstet & Gynaecol, Program Dev & Fetal Hlth, Toronto, ON M5G 1X5, Canada Mt Sinai Hosp Toronto ON Canada M5G 1X5 Hlth, Toronto, ON M5G 1X5, Canada Univ Toronto, Hosp Sick Children, Res Inst, Dept Pediat, Toronto, ON M5G 1X8, Canada Univ Toronto Toronto ON Canada M5G 1X8 ediat, Toronto, ON M5G 1X8, Canada Univ Toronto, Dept Physiol, Toronto, ON, Canada Univ Toronto Toronto ON Canada oronto, Dept Physiol, Toronto, ON, Canada Univ Zurich Irchel, Inst Physiol, CH-8057 Zurich, Switzerland Univ Zurich Irchel Zurich Switzerland CH-8057 H-8057 Zurich, Switzerland
Titolo Testata:
JOURNAL OF CLINICAL INVESTIGATION
fascicolo: 5, volume: 105, anno: 2000,
pagine: 577 - 587
SICI:
0021-9738(200003)105:5<577:HFMTBE>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN CYTOTROPHOBLAST DIFFERENTIATION; ENDOTHELIAL GROWTH-FACTOR; ENDOVASCULAR INVASION; ERYTHROPOIETIN GENE; VILLOUS EXPLANTS; IN-VITRO; PREECLAMPSIA; PROTEIN; EXPRESSION; ACTIVATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Caniggia, I Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Obstet & Gynaecol, Program Dev & Fetal Hlth, 600 Univ Ave, Toronto, ON M5G 1X5, Canada Mt Sinai Hosp 600 Univ Ave Toronto ON Canada M5G 1X5 5, Canada
Citazione:
I. Caniggia et al., "Hypoxia-inducible factor-1 mediates the biological effects of oxygen on human trophoblast differentiation through TGF beta(3)", J CLIN INV, 105(5), 2000, pp. 577-587

Abstract

During early pregnancy, placentation occurs in a relatively hypoxic environment that is essential for appropriate embryonic development. Intervillousblood flow increases around 10 to 12 weeks of gestation and results in exposure of trophoblast cells to increased oxygen tension. Before this time, low oxygen appears to prevent trophoblast differentiation toward an invasivephenotype. Using human villous explants of 5-8 weeks' gestation, we found that low oxygen tension triggered trophoblast proliferation, fibronectin synthesis, alpha(5) integrin expression, and gelatinase A activity. These biochemical markers were barely detectable under oxic conditions. We thereforeexamined the placental expression of hypoxia-inducible factor-1 (HIF-1), amaster regulator of oxygen homeostasis, and determined that expression of HIF-1 alpha subunit during the first trimester of gestation parallels that of TGF beta(3), an inhibitor of extravillous trophoblast differentiation. Expression of both molecules is high in early pregnancy and falls around 9 weeks of gestation, when placental pO(2) levels are believed to increase. Increasing oxygen tension induced a similar decrease in expression in cultured explants. Moreover, antisense inhibition of HIF-1 alpha expression in hypoxic explants inhibited expression of TGF beta(3), arrested cell proliferation, decreased alpha(5) expression and gelatinase A activity, and triggeredbiochemical markers of an invasive trophoblast phenotype such as alpha(1) integrin and gelatinase B expression. These data suggest that the oxygen-regulated early events of trophoblast differentiation are in part mediated byTGF beta(3) through HIF-1 transcription factors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 20:02:46