Placental growth factor (PlGF), abundantly produced from trophoblasts is involved in placental angiogenesis. The regulatory mechanism of its expression is poorly understood. Hypoxia inducible factors (HIFs) are centrally involved in the modulation of cellular function in response to low oxygen conditions. This study aimed to clarify HIF1 alpha and HIF2 alpha expression patterns during cytotrophoblast differentiation into syncytiotrophoblast and the impact of any changes on PlGF expression. HIF proteins were induced remarkably under low oxygen condition (2%). HIF1 alpha expression decreased and HIF2 alpha expression increased when syncytialization of cultured cytotrophoblasts is progressed. Those expression changes of HIF proteins in the process of in-vitro syncytialization was congruent with the immunohistochemical findings in preeclamptic placenta as well as uncomplicated placenta. Low oxygen condition was also associated with reduced PlGF production in syncytializing primary cells and BeWo choriocarcinoma cells. Small interfering RNA-mediated HIF2 alpha knockdown in BeWo cells abrogated hypoxia-associated decreases in PlGF secretion; HIF1 alpha silencing had no significant effect on PlGF secretion. In summary, HIF2 alpha, rather than HIF1a, is most affected by reduced oxygen level during syncytialization and increases in HIF2 alpha trigger a reduction of PlGF production. Our findings suggest new and important connections between HIF proteins and PlGF pathways in the regulation of placental angiogenesis.
机构:
Univ Adelaide, Discipline Obstet & Gynaecol, Res Ctr Reprod Hlth, Adelaide, SA, Australia
Univ Colombo, Fac Med, Dept Anat & Human Genet, Colombo, Sri LankaUniv Adelaide, Discipline Obstet & Gynaecol, Res Ctr Reprod Hlth, Adelaide, SA, Australia
Andraweera, P. H.
Dekker, G. A.
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Univ Adelaide, Discipline Obstet & Gynaecol, Res Ctr Reprod Hlth, Adelaide, SA, Australia
Lyell McEwin Hosp, Womens & Childrens Div, Elizabeth Vale, SA, AustraliaUniv Adelaide, Discipline Obstet & Gynaecol, Res Ctr Reprod Hlth, Adelaide, SA, Australia
Dekker, G. A.
Laurence, J. A.
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Univ Adelaide, Discipline Obstet & Gynaecol, Res Ctr Reprod Hlth, Adelaide, SA, AustraliaUniv Adelaide, Discipline Obstet & Gynaecol, Res Ctr Reprod Hlth, Adelaide, SA, Australia
Laurence, J. A.
Roberts, C. T.
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Univ Adelaide, Discipline Obstet & Gynaecol, Res Ctr Reprod Hlth, Adelaide, SA, AustraliaUniv Adelaide, Discipline Obstet & Gynaecol, Res Ctr Reprod Hlth, Adelaide, SA, Australia
机构:
Ohio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med,Coll Med, Columbus, OH 43210 USAOhio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med,Coll Med, Columbus, OH 43210 USA
Eubank, Tim D.
Roda, Julie M.
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Ohio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med,Coll Med, Columbus, OH 43210 USAOhio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med,Coll Med, Columbus, OH 43210 USA
Roda, Julie M.
Liu, Haowen
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Ohio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med,Coll Med, Columbus, OH 43210 USAOhio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med,Coll Med, Columbus, OH 43210 USA
Liu, Haowen
O'Neil, Todd
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Ohio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med,Coll Med, Columbus, OH 43210 USAOhio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med,Coll Med, Columbus, OH 43210 USA
O'Neil, Todd
Marsh, Clay B.
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Ohio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med,Coll Med, Columbus, OH 43210 USAOhio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med,Coll Med, Columbus, OH 43210 USA
机构:
Univ Calif San Francisco, Div Maternal Fetal Med, Ctr Reprod Sci, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Dept Anat, San Francisco, CA 94143 USAUniv Calif San Francisco, Div Maternal Fetal Med, Ctr Reprod Sci, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
机构:
Univ Adelaide, Discipline Obstet & Gynaecol, Res Ctr Reprod Hlth, Adelaide, SA, Australia
Univ Colombo, Fac Med, Dept Anat & Human Genet, Colombo, Sri LankaUniv Adelaide, Discipline Obstet & Gynaecol, Res Ctr Reprod Hlth, Adelaide, SA, Australia
Andraweera, P. H.
Dekker, G. A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Adelaide, Discipline Obstet & Gynaecol, Res Ctr Reprod Hlth, Adelaide, SA, Australia
Lyell McEwin Hosp, Womens & Childrens Div, Elizabeth Vale, SA, AustraliaUniv Adelaide, Discipline Obstet & Gynaecol, Res Ctr Reprod Hlth, Adelaide, SA, Australia
Dekker, G. A.
Laurence, J. A.
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h-index: 0
机构:
Univ Adelaide, Discipline Obstet & Gynaecol, Res Ctr Reprod Hlth, Adelaide, SA, AustraliaUniv Adelaide, Discipline Obstet & Gynaecol, Res Ctr Reprod Hlth, Adelaide, SA, Australia
Laurence, J. A.
Roberts, C. T.
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h-index: 0
机构:
Univ Adelaide, Discipline Obstet & Gynaecol, Res Ctr Reprod Hlth, Adelaide, SA, AustraliaUniv Adelaide, Discipline Obstet & Gynaecol, Res Ctr Reprod Hlth, Adelaide, SA, Australia
机构:
Ohio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med,Coll Med, Columbus, OH 43210 USAOhio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med,Coll Med, Columbus, OH 43210 USA
Eubank, Tim D.
Roda, Julie M.
论文数: 0引用数: 0
h-index: 0
机构:
Ohio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med,Coll Med, Columbus, OH 43210 USAOhio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med,Coll Med, Columbus, OH 43210 USA
Roda, Julie M.
Liu, Haowen
论文数: 0引用数: 0
h-index: 0
机构:
Ohio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med,Coll Med, Columbus, OH 43210 USAOhio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med,Coll Med, Columbus, OH 43210 USA
Liu, Haowen
O'Neil, Todd
论文数: 0引用数: 0
h-index: 0
机构:
Ohio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med,Coll Med, Columbus, OH 43210 USAOhio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med,Coll Med, Columbus, OH 43210 USA
O'Neil, Todd
Marsh, Clay B.
论文数: 0引用数: 0
h-index: 0
机构:
Ohio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med,Coll Med, Columbus, OH 43210 USAOhio State Univ, Dorothy M Davis Heart & Lung Res Inst, Div Pulm Allergy Crit Care & Sleep Med, Dept Internal Med,Coll Med, Columbus, OH 43210 USA
机构:
Univ Calif San Francisco, Div Maternal Fetal Med, Ctr Reprod Sci, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Dept Anat, San Francisco, CA 94143 USAUniv Calif San Francisco, Div Maternal Fetal Med, Ctr Reprod Sci, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA