Estrogen-Related Receptor γ Serves a Role in Blood Pressure Homeostasis During Pregnancy
被引:23
作者:
Luo, Yanmin
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Univ Texas SW Med Ctr Dallas, North Texas March Dimes Birth Defects Ctr, Dept Biochem, Dallas, TX 75390 USA
Sun Yat Sen Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Guangzhou 510080, Guangdong, Peoples R ChinaUniv Texas SW Med Ctr Dallas, North Texas March Dimes Birth Defects Ctr, Dept Biochem, Dallas, TX 75390 USA
Luo, Yanmin
[1
,2
]
Kumar, Premlata
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Univ Texas SW Med Ctr Dallas, North Texas March Dimes Birth Defects Ctr, Dept Biochem, Dallas, TX 75390 USAUniv Texas SW Med Ctr Dallas, North Texas March Dimes Birth Defects Ctr, Dept Biochem, Dallas, TX 75390 USA
Kumar, Premlata
[1
]
Chen, Chien-Cheng
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Univ Texas SW Med Ctr Dallas, North Texas March Dimes Birth Defects Ctr, Dept Biochem, Dallas, TX 75390 USAUniv Texas SW Med Ctr Dallas, North Texas March Dimes Birth Defects Ctr, Dept Biochem, Dallas, TX 75390 USA
Chen, Chien-Cheng
[1
]
Latham, Jordan
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Univ Texas SW Med Ctr Dallas, North Texas March Dimes Birth Defects Ctr, Dept Biochem, Dallas, TX 75390 USAUniv Texas SW Med Ctr Dallas, North Texas March Dimes Birth Defects Ctr, Dept Biochem, Dallas, TX 75390 USA
Latham, Jordan
[1
]
Wang, Lei
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Univ Texas SW Med Ctr Dallas, North Texas March Dimes Birth Defects Ctr, Dept Biochem, Dallas, TX 75390 USAUniv Texas SW Med Ctr Dallas, North Texas March Dimes Birth Defects Ctr, Dept Biochem, Dallas, TX 75390 USA
Wang, Lei
[1
]
Tudela, Carmen
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Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USAUniv Texas SW Med Ctr Dallas, North Texas March Dimes Birth Defects Ctr, Dept Biochem, Dallas, TX 75390 USA
Tudela, Carmen
[3
]
Alexander, James M.
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Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USAUniv Texas SW Med Ctr Dallas, North Texas March Dimes Birth Defects Ctr, Dept Biochem, Dallas, TX 75390 USA
Alexander, James M.
[3
]
Shelton, John M.
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Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USAUniv Texas SW Med Ctr Dallas, North Texas March Dimes Birth Defects Ctr, Dept Biochem, Dallas, TX 75390 USA
Shelton, John M.
[4
]
McKown, Leslie
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Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USAUniv Texas SW Med Ctr Dallas, North Texas March Dimes Birth Defects Ctr, Dept Biochem, Dallas, TX 75390 USA
McKown, Leslie
[4
]
Mendelson, Carole R.
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Univ Texas SW Med Ctr Dallas, North Texas March Dimes Birth Defects Ctr, Dept Biochem, Dallas, TX 75390 USA
Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USAUniv Texas SW Med Ctr Dallas, North Texas March Dimes Birth Defects Ctr, Dept Biochem, Dallas, TX 75390 USA
Mendelson, Carole R.
[1
,3
]
机构:
[1] Univ Texas SW Med Ctr Dallas, North Texas March Dimes Birth Defects Ctr, Dept Biochem, Dallas, TX 75390 USA
[2] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Guangzhou 510080, Guangdong, Peoples R China
[3] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA
[4] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA
Persistent hypoxia caused by shallow trophoblast invasion and poor placental perfusion may underlie the pathophysiology of preeclampsia, a leading cause of maternal and neonatal morbidity and mortality. Previously, we found that estrogen-related receptor gamma (ERR gamma) serves a critical and O-2-dependent role in differentiation of human trophoblasts in culture and expression of tissue kallikrein and voltage-gated K+ channels. In this study, we surprisingly observed that ERR gamma expression was significantly increased in placentas from preeclamptic women compared with that in gestation-matched normotensive women. To further investigate a functional role for ERR gamma during pregnancy, we analyzed ERR gamma-deficient mice. Maternal systolic blood pressure was significantly reduced in pregnant ERR gamma(+/-) females bred to ERR gamma(+/-) males compared with that in wild-type (WT) mice and was markedly up-regulated by treatment of WT pregnant mice with the ERR gamma agonist DY131. Placentas of ERR gamma(+/-) mice manifested increased vascular endothelial growth factor A expression compared with that in WT mice. Notably, circulating levels of the antiangiogenic factor, soluble fms-like tyrosine kinase-1, were significantly reduced in ERR gamma(+/-) pregnant mice as was serum aldosterone. These effects were associated with a decrease in maternal adrenal Cyp11b1 (steroid 11 beta-hydroxylase) and Cyp11b2 (aldosterone synthase) expression. In contrast, adrenal Cyp11b1 and Cyp11b2 mRNA were increased in pregnant WT mice treated with DY131. Moreover, chromatin immunoprecipitation and luciferase reporter assays identified Cyp11b2 as a transcriptional target of ERR gamma. Collectively, these findings reveal a potential role of ERR gamma in maternal blood pressure homeostasis during pregnancy and suggest that aberrant ERR gamma expression may contribute to the pathogenesis of preeclampsia.
机构:
Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Alaynick, William A.
Way, James M.
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h-index: 0
机构:
GlaxoSmithKline, Res & Dev, Res Triangle Pk, NC 27709 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Way, James M.
Wilson, Stephanie A.
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h-index: 0
机构:
GlaxoSmithKline, Res & Dev, Res Triangle Pk, NC 27709 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Wilson, Stephanie A.
Benson, William G.
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h-index: 0
机构:
GlaxoSmithKline, Res & Dev, Res Triangle Pk, NC 27709 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Benson, William G.
Pei, Liming
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机构:
Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Pei, Liming
Downes, Michael
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机构:
Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Downes, Michael
Yu, Ruth
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机构:
Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Yu, Ruth
Jonker, Johan W.
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机构:
Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Jonker, Johan W.
Holt, Jason A.
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机构:
GlaxoSmithKline, Res & Dev, Res Triangle Pk, NC 27709 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Holt, Jason A.
Rajpal, Deepak K.
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GlaxoSmithKline, Res & Dev, Res Triangle Pk, NC 27709 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Rajpal, Deepak K.
Li, Hao
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机构:
GlaxoSmithKline, Res & Dev, Res Triangle Pk, NC 27709 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Li, Hao
Stuart, Joan
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机构:
GlaxoSmithKline, Res & Dev, Res Triangle Pk, NC 27709 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Stuart, Joan
McPherson, Ruth
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机构:
Univ Ottawa, Inst Heart, Atherogen Lab, Ottawa, ON K1Y 4W7, CanadaSalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
McPherson, Ruth
Remlinger, Katja S.
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机构:
GlaxoSmithKline, Res & Dev, Res Triangle Pk, NC 27709 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Remlinger, Katja S.
Chang, Ching-Yi
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机构:
Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Chang, Ching-Yi
McDonnell, Donald P.
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机构:
Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
McDonnell, Donald P.
Evans, Ronald M.
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机构:
Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Evans, Ronald M.
Billin, Andrew N.
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h-index: 0
机构:
GlaxoSmithKline, Res & Dev, Res Triangle Pk, NC 27709 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
机构:
Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Alaynick, William A.
Way, James M.
论文数: 0引用数: 0
h-index: 0
机构:
GlaxoSmithKline, Res & Dev, Res Triangle Pk, NC 27709 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Way, James M.
Wilson, Stephanie A.
论文数: 0引用数: 0
h-index: 0
机构:
GlaxoSmithKline, Res & Dev, Res Triangle Pk, NC 27709 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Wilson, Stephanie A.
Benson, William G.
论文数: 0引用数: 0
h-index: 0
机构:
GlaxoSmithKline, Res & Dev, Res Triangle Pk, NC 27709 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Benson, William G.
Pei, Liming
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h-index: 0
机构:
Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Pei, Liming
Downes, Michael
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h-index: 0
机构:
Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Downes, Michael
Yu, Ruth
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机构:
Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Yu, Ruth
Jonker, Johan W.
论文数: 0引用数: 0
h-index: 0
机构:
Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Jonker, Johan W.
Holt, Jason A.
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h-index: 0
机构:
GlaxoSmithKline, Res & Dev, Res Triangle Pk, NC 27709 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Holt, Jason A.
Rajpal, Deepak K.
论文数: 0引用数: 0
h-index: 0
机构:
GlaxoSmithKline, Res & Dev, Res Triangle Pk, NC 27709 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Rajpal, Deepak K.
Li, Hao
论文数: 0引用数: 0
h-index: 0
机构:
GlaxoSmithKline, Res & Dev, Res Triangle Pk, NC 27709 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Li, Hao
Stuart, Joan
论文数: 0引用数: 0
h-index: 0
机构:
GlaxoSmithKline, Res & Dev, Res Triangle Pk, NC 27709 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Stuart, Joan
McPherson, Ruth
论文数: 0引用数: 0
h-index: 0
机构:
Univ Ottawa, Inst Heart, Atherogen Lab, Ottawa, ON K1Y 4W7, CanadaSalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
McPherson, Ruth
Remlinger, Katja S.
论文数: 0引用数: 0
h-index: 0
机构:
GlaxoSmithKline, Res & Dev, Res Triangle Pk, NC 27709 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Remlinger, Katja S.
Chang, Ching-Yi
论文数: 0引用数: 0
h-index: 0
机构:
Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Chang, Ching-Yi
McDonnell, Donald P.
论文数: 0引用数: 0
h-index: 0
机构:
Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
McDonnell, Donald P.
Evans, Ronald M.
论文数: 0引用数: 0
h-index: 0
机构:
Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
Evans, Ronald M.
Billin, Andrew N.
论文数: 0引用数: 0
h-index: 0
机构:
GlaxoSmithKline, Res & Dev, Res Triangle Pk, NC 27709 USASalk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA