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Titolo:
Inhibition of TGF-beta(3) restores the invasive capability of extravilloustrophoblasts in preeclamptic pregnancies
Autore:
Caniggia, I; Grisaru-Gravnosky, S; Kuliszewsky, M; Post, M; Lye, SJ;
Indirizzi:
Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Program Fetal Hlth & Dev, Toronto, ON M5G 1X5, Canada Mt Sinai Hosp Toronto ON Canada M5G 1X5 Dev, Toronto, ON M5G 1X5, Canada Univ Toronto, Hosp Sick Children, Dept Obstet & Gynaecol, Toronto, ON M5G 1X8, Canada Univ Toronto Toronto ON Canada M5G 1X8 aecol, Toronto, ON M5G 1X8, Canada Univ Toronto, Hosp Sick Children, Dept Physiol, Toronto, ON M5G 1X8, Canada Univ Toronto Toronto ON Canada M5G 1X8 ysiol, Toronto, ON M5G 1X8, Canada Univ Toronto, Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, CanadaUniv Toronto Toronto ON Canada M5G 1X8 ediat, Toronto, ON M5G 1X8, Canada Univ Toronto, Hosp Sick Children, Div Neonatol Res, Toronto, ON M5G 1X8, Canada Univ Toronto Toronto ON Canada M5G 1X8 l Res, Toronto, ON M5G 1X8, Canada
Titolo Testata:
JOURNAL OF CLINICAL INVESTIGATION
fascicolo: 12, volume: 103, anno: 1999,
pagine: 1641 - 1650
SICI:
0021-9738(199906)103:12<1641:IOTRTI>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN CYTOTROPHOBLASTS; ENDOVASCULAR INVASION; ALTERED EXPRESSION; TGF-BETA; DIFFERENTIATION; FIBRONECTIN; PLACENTA; BINDING; IMPLANTATION; LOCALIZATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Caniggia, I Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Program Fetal Hlth &Dev, 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., "Inhibition of TGF-beta(3) restores the invasive capability of extravilloustrophoblasts in preeclamptic pregnancies", J CLIN INV, 103(12), 1999, pp. 1641-1650

Abstract

Preeclampsia, the major cause of maternal morbidity and mortality in developed countries, is associated with abnormalities of placenta function due to shallow invasion of the maternal decidua by trophoblasts. Data suggest that TGF-beta may play a role in inhibiting trophoblast outgrowth or invasion, or both. We report that placental TGF-beta(3) expression is high in earlypregnancy but falls at around 9 weeks' gestation. This pattern is inversely correlated with trophoblast outgrowth and fibronectin synthesis, markers of early trophoblast differentiation toward an invasive phenotype. We demonstrate that TGF-beta(3) is overexpressed in preeclamptic placentae. In contrast to control placentae, explants from preeclamptic pregnancies fail to exhibit spontaneous invasion in vitro. Significantly, antisense-induced inhibition of TGF-beta(3) expression, and inhibition of TGF-beta(3) activity with antibodies, induces the formation of columns of trophoblast cells, whichmigrate out oft:he explant into the underlying Matrigel. To our knowledge,this is the first demonstration that the hypoinvasive placental phenotype characteristic of preeclampsia can be essentially normalized in vitro by biochemical manipulation. We speculate that a failure to downregulate expression of TGF-beta(3) at around 9 weeks' gestation results in shallow trophoblast invasion and predisposes the pregnancy to preeclampsia.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 19:30:59