Maternal hepatic growth response to pregnancy in the mouse

被引:37
作者
Dai, Guoli [1 ]
Bustamante, Juan J. [2 ]
Zou, Yuhong [1 ]
Myronovych, Andriy [1 ]
Bao, Qi [1 ]
Kumar, Sudhanshu [1 ]
Soares, Michael J. [3 ]
机构
[1] Indiana Univ Purdue Univ, Ctr Regenerat Biol & Med, Sch Sci, Indianapolis, IN 46202 USA
[2] Texas A&M Hlth Sci Ctr, Dept Pharmaceut Sci, Kingsville, TX 78363 USA
[3] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Inst Reprod Hlth & Regenerat Med, Kansas City, KS 66160 USA
基金
美国安德鲁·梅隆基金会;
关键词
hepatocyte proliferation; liver growth; pregnancy; DEFICIENT LIVER-REGENERATION; NECROSIS-FACTOR RECEPTOR; INDUCED DNA-SYNTHESIS; MICE LACKING TYPE-1; BETA-CELL MASS; NUCLEAR RECEPTOR; HEPATOCYTE PROLIFERATION; SIGNALING PATHWAY; ETHINYL ESTRADIOL; DRUG-METABOLISM;
D O I
10.1258/ebm.2011.011076
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Pregnancy is characterized by physiological adjustments in the maternal compartment. In this investigation, the influence of pregnancy on maternal liver was examined in CD-1 mice. Dramatic changes were observed in the size of the maternal liver during pregnancy. Livers doubled in weight from the non-pregnant state to day 18 of pregnancy. The pregnancy-induced hepatomegaly was a physiological event of liver growth confirmed by DNA content increase and detection of hepatocyte hyperplasia and hypertrophy. Growth of the liver was initiated following implantation and peaked at parturition. The expression and/or activities of key genes known to regulate liver regeneration, a phenomenon of liver growth compensatory to liver mass loss, were investigated. The results showed that pregnancy-dependent liver growth was associated with interleukin (IL)-6, tumor necrosis factor alpha, c-Jun and IL-1 beta, but independent of hepatocyte growth factor, fibroblast growth factor 1, tumor necrosis factor receptor 1, constitutive androstane receptor and pregnane X receptor. Furthermore, maternal liver growth was associated with the activation of hepatic signal transducer and activator of transcription 3, beta-catenin and epidermal growth factor receptor, but pregnancy did not activate hepatic c-Met. The findings suggest that the molecular mechanisms regulating pregnancy-induced liver growth and injury-induced liver regeneration exhibit overlapping features but are not identical. In summary, the liver of the mouse adapts to the demands of pregnancy via a dramatic growth response driven by hepatocyte proliferation and size increase.
引用
收藏
页码:1322 / 1332
页数:11
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