Hypoxia Inducible Factor 1 Alpha Regulates Matrigel-induced Endovascular Differentiation under Normoxia in a Human Extravillous Trophoblast Cell Line

K. Fukushima, Masaharu Murata, Masahiro Hachisuga, K. Tsukimori, H. Seki, S. Takeda, Kazuo Asanoma, N. Wake

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Extravillous trophoblast (EVT) cells mimic endothelial cells during angiogenesis, inducing remodeling of the spiral arteries that increases blood flow toward the intravillous space. We have previously shown that signals involving the vascular endothelial growth factor (VEGF) axis are essential for endovascular differentiation through integrin signaling from the extracellular matrix: This was accomplished with use of the human EVT cell line TCL1, which shows tube formation that specifically recalls morphological changes in endothelial cells. To investigate endovascular differentiation in EVT further, we investigated the role of hypoxia inducible factor (HIF)1A, a subunit of HIF1 transcription factor that regulates not only adaptive responses to hypoxia, but also many cellular functions under normoxia, which was up-regulated in DNA microarray analysis during matrigel-induced endovascular differentiation under normoxia. HIF1A induces VEGF and ITGAV/ITGB3 aggregation, actions known to be important for cellular survival and endovascular differentiation in EVT. Inhibition of HIF1A up-regulation using siRNA introduction or chemical inhibition suppressed hypoxia-responsive element transcriptional activity, VEGF induction, ITGAV/ITGB3 aggregation accompanied by the inhibition of tube formation in TCL1 cells. These results suggest that HIF1A has a crucial role in regulating EVT behavior including matrigel-induced endovascular differentiation under normoxia.

Original languageEnglish
Pages (from-to)324-331
Number of pages8
JournalPlacenta
Volume29
Issue number4
DOIs
Publication statusPublished - Apr 1 2008

Fingerprint

Hypoxia-Inducible Factor 1
Trophoblasts
Cell Line
Vascular Endothelial Growth Factor A
Endothelial Cells
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Integrins
Small Interfering RNA
Extracellular Matrix
Transcription Factors
Up-Regulation
Arteries
matrigel
Survival
Inhibition (Psychology)
Hypoxia

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Obstetrics and Gynaecology
  • Developmental Biology

Cite this

Hypoxia Inducible Factor 1 Alpha Regulates Matrigel-induced Endovascular Differentiation under Normoxia in a Human Extravillous Trophoblast Cell Line. / Fukushima, K.; Murata, Masaharu; Hachisuga, Masahiro; Tsukimori, K.; Seki, H.; Takeda, S.; Asanoma, Kazuo; Wake, N.

In: Placenta, Vol. 29, No. 4, 01.04.2008, p. 324-331.

Research output: Contribution to journalArticle

Fukushima, K. ; Murata, Masaharu ; Hachisuga, Masahiro ; Tsukimori, K. ; Seki, H. ; Takeda, S. ; Asanoma, Kazuo ; Wake, N. / Hypoxia Inducible Factor 1 Alpha Regulates Matrigel-induced Endovascular Differentiation under Normoxia in a Human Extravillous Trophoblast Cell Line. In: Placenta. 2008 ; Vol. 29, No. 4. pp. 324-331.
@article{65d5f5524731432781b3c2f6c7325580,
title = "Hypoxia Inducible Factor 1 Alpha Regulates Matrigel-induced Endovascular Differentiation under Normoxia in a Human Extravillous Trophoblast Cell Line",
abstract = "Extravillous trophoblast (EVT) cells mimic endothelial cells during angiogenesis, inducing remodeling of the spiral arteries that increases blood flow toward the intravillous space. We have previously shown that signals involving the vascular endothelial growth factor (VEGF) axis are essential for endovascular differentiation through integrin signaling from the extracellular matrix: This was accomplished with use of the human EVT cell line TCL1, which shows tube formation that specifically recalls morphological changes in endothelial cells. To investigate endovascular differentiation in EVT further, we investigated the role of hypoxia inducible factor (HIF)1A, a subunit of HIF1 transcription factor that regulates not only adaptive responses to hypoxia, but also many cellular functions under normoxia, which was up-regulated in DNA microarray analysis during matrigel-induced endovascular differentiation under normoxia. HIF1A induces VEGF and ITGAV/ITGB3 aggregation, actions known to be important for cellular survival and endovascular differentiation in EVT. Inhibition of HIF1A up-regulation using siRNA introduction or chemical inhibition suppressed hypoxia-responsive element transcriptional activity, VEGF induction, ITGAV/ITGB3 aggregation accompanied by the inhibition of tube formation in TCL1 cells. These results suggest that HIF1A has a crucial role in regulating EVT behavior including matrigel-induced endovascular differentiation under normoxia.",
author = "K. Fukushima and Masaharu Murata and Masahiro Hachisuga and K. Tsukimori and H. Seki and S. Takeda and Kazuo Asanoma and N. Wake",
year = "2008",
month = "4",
day = "1",
doi = "10.1016/j.placenta.2008.01.006",
language = "English",
volume = "29",
pages = "324--331",
journal = "Placenta",
issn = "0143-4004",
publisher = "W.B. Saunders Ltd",
number = "4",

}

TY - JOUR

T1 - Hypoxia Inducible Factor 1 Alpha Regulates Matrigel-induced Endovascular Differentiation under Normoxia in a Human Extravillous Trophoblast Cell Line

AU - Fukushima, K.

AU - Murata, Masaharu

AU - Hachisuga, Masahiro

AU - Tsukimori, K.

AU - Seki, H.

AU - Takeda, S.

AU - Asanoma, Kazuo

AU - Wake, N.

PY - 2008/4/1

Y1 - 2008/4/1

N2 - Extravillous trophoblast (EVT) cells mimic endothelial cells during angiogenesis, inducing remodeling of the spiral arteries that increases blood flow toward the intravillous space. We have previously shown that signals involving the vascular endothelial growth factor (VEGF) axis are essential for endovascular differentiation through integrin signaling from the extracellular matrix: This was accomplished with use of the human EVT cell line TCL1, which shows tube formation that specifically recalls morphological changes in endothelial cells. To investigate endovascular differentiation in EVT further, we investigated the role of hypoxia inducible factor (HIF)1A, a subunit of HIF1 transcription factor that regulates not only adaptive responses to hypoxia, but also many cellular functions under normoxia, which was up-regulated in DNA microarray analysis during matrigel-induced endovascular differentiation under normoxia. HIF1A induces VEGF and ITGAV/ITGB3 aggregation, actions known to be important for cellular survival and endovascular differentiation in EVT. Inhibition of HIF1A up-regulation using siRNA introduction or chemical inhibition suppressed hypoxia-responsive element transcriptional activity, VEGF induction, ITGAV/ITGB3 aggregation accompanied by the inhibition of tube formation in TCL1 cells. These results suggest that HIF1A has a crucial role in regulating EVT behavior including matrigel-induced endovascular differentiation under normoxia.

AB - Extravillous trophoblast (EVT) cells mimic endothelial cells during angiogenesis, inducing remodeling of the spiral arteries that increases blood flow toward the intravillous space. We have previously shown that signals involving the vascular endothelial growth factor (VEGF) axis are essential for endovascular differentiation through integrin signaling from the extracellular matrix: This was accomplished with use of the human EVT cell line TCL1, which shows tube formation that specifically recalls morphological changes in endothelial cells. To investigate endovascular differentiation in EVT further, we investigated the role of hypoxia inducible factor (HIF)1A, a subunit of HIF1 transcription factor that regulates not only adaptive responses to hypoxia, but also many cellular functions under normoxia, which was up-regulated in DNA microarray analysis during matrigel-induced endovascular differentiation under normoxia. HIF1A induces VEGF and ITGAV/ITGB3 aggregation, actions known to be important for cellular survival and endovascular differentiation in EVT. Inhibition of HIF1A up-regulation using siRNA introduction or chemical inhibition suppressed hypoxia-responsive element transcriptional activity, VEGF induction, ITGAV/ITGB3 aggregation accompanied by the inhibition of tube formation in TCL1 cells. These results suggest that HIF1A has a crucial role in regulating EVT behavior including matrigel-induced endovascular differentiation under normoxia.

UR - http://www.scopus.com/inward/record.url?scp=40949102138&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40949102138&partnerID=8YFLogxK

U2 - 10.1016/j.placenta.2008.01.006

DO - 10.1016/j.placenta.2008.01.006

M3 - Article

C2 - 18342368

AN - SCOPUS:40949102138

VL - 29

SP - 324

EP - 331

JO - Placenta

JF - Placenta

SN - 0143-4004

IS - 4

ER -