Mechanisms for increased expression of cholesterol 7alpha-hydroxylase (Cyp7a1) in lactating rats.
Mechanisms for increased expression of cholesterol 7alpha-hydroxylase (Cyp7a1) in lactating rats.
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DOI：
10.1002/hep.23289
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发表时间：
2010-01
期刊：
影响因子：
13.5
通讯作者：
Vore, Mary
中科院分区：
文献类型：
--
作者：
Wooton-Kee, Clavia Ruth;Coy, Donna J.;Athippozhy, Antony T.;Zhao, Tianyong;Jones, Brett R.;Vore, Mary
Cholesterol 7α-hydroxylase (Cyp7a1) and the bile acid pool size are increased 2–3 fold in lactating postpartum rats. We investigated the interaction of nuclear receptors with the Cyp7a1 proximal promoter and the expression of regulatory signaling pathways in postpartum rats at day 10 (PPd10) vs female controls to identify the mechanisms of increased expression of Cyp7a1, which is maximal at 16 h. Liver X receptor (LXRα) and RNA Polymerase II (RNA Pol II) recruitment to Cyp7a1 chromatin were increased 1.5- and 2.5-fold, respectively, at 16 h on PPd10. Expression of nuclear receptors farnesoid X receptor (FXR), LXRα, liver receptor homologue (LRH-1), hepatocyte nuclear factor 4α (HNF4α), and short heterodimer partner (SHP) mRNA and co-activator peroxisome proliferators-activated receptor γ coactivator-1α (PGC-1α) mRNA was unchanged in PPd10 vs controls at 16 h, while chicken ovalbumin upstream transcription factor II (COUP-TFII) was decreased 40% at 16 h. Investigation of a repressive signaling pathway, the cJun-N-terminal kinase (JNK) signaling pathway in PPd10 vs controls, showed decreased mRNA expression of hepatocyte growth factor (HGF; decreased 60% at 16 h) and tyrosine kinase receptor cMet (decreased 44–50% at 16 h), but these were not accompanied by decreased expression of phosphorylated c-Jun. Importantly, expression of Fibroblast Growth Factor 15 (FGF15) mRNA in the ileum was decreased 70% in PPd10 vs controls, while phosphorylated mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (Erk1/2) protein expression in liver was decreased 88% at 16 h. The increased recruitment of LXRα, a Cyp7a1 stimulatory pathway, and decreased expression of FGF15 and phosphorylated Erk1/2, a Cyp7a1 repressive pathway, combined to increase Cyp7a1 expression during lactation.
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影响因子：
4.1
作者：
GIBBONS, GF;PULLINGER, CR;WILLIAMSON, DH
通讯作者：
WILLIAMSON, DH
影响因子：
3.5
作者：
Chiang, JYL;Kimmel, R;Stroup, D
通讯作者：
Stroup, D
影响因子：
13.5
作者：
Mitro, Nico;Godio, Cristina;Crestani, Maurizio
通讯作者：
Crestani, Maurizio
DOI：
10.1152/ajpgi.00309.2001
发表时间：
2002-01-01
影响因子：
4.5
作者：
Mottino, AD;Hoffman, T;Vore, M
通讯作者：
Vore, M
DOI：
10.1152/ajpgi.2001.280.6.g1261
发表时间：
2001-06-01
影响因子：
4.5
作者：
Mottino, AD;Hoffman, T;Vore, M
通讯作者：
Vore, M