The role of H19, a long non-coding RNA, in mouse liver postnatal maturation.
The role of H19, a long non-coding RNA, in mouse liver postnatal maturation.
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DOI：
10.1371/journal.pone.0187557
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Zhong XB
中科院分区：
文献类型：
--
作者：
Pope C;Piekos SC;Chen L;Mishra S;Zhong XB
H19 RNA在出生后早期高度表达，并在特定时间急剧下降，与成熟肝功能重要基因（如药物代谢酶）的表达增加相对应。H19在调节肝脏成熟中的作用目前尚不清楚。利用H19敲除小鼠模型来确定H19在肝脏发育中的作用，我们量化了胰岛素生长因子信号、Wnt信号、关键细胞色素P450 （P450）酶的基因表达，这些酶会随着肝脏的发育而改变，以及肝脏中产生的胎儿和成人血浆蛋白。在缺乏H19表达的小鼠中，出生后肝脏重量显著增加，活跃增殖细胞数量显著增加。细胞增殖的增加可能是由于影响Wnt信号的β-catenin蛋白的增加，胰岛素样生长因子2 （IGF2）表达的增加，和/或胰岛素样生长因子1受体（IGF1R）在蛋白水平上表达的增加。microRNA 675 （miR-675）失去对IGF1R的靶向抑制可能是IGF1R增加的原因，因为在我们的模型中，miR-675的表达也随着H19表达的丧失而消失。P450的表达模式基本不变。没有发现血浆蛋白产生变化，这表明H19可能对肝脏成熟并不重要，尽管它在肝脏生长过程中控制细胞增殖。H19可能对正常肝脏发育很重要，了解肝脏如何成熟将有助于预测儿科人群的药物疗效和毒性。
H19 RNA is highly expressed at early postnatal ages and precipitously decreases at a specific time corresponding with increases in expression of genes important for mature liver function, such as drug metabolizing enzymes. H19’s role in the regulation of liver maturation is currently unknown. Using an H19 knockout mouse model to determine the role of H19 in liver development, we quantified gene expression for insulin growth factor signaling, Wnt signaling, key cytochrome P450 (P450) enzymes known to change as the liver develops, and fetal and adult plasma protein produced in liver. In mice lacking H19 expression, liver weights were significantly increased immediately after birth and significant increases were found in the number of actively proliferating cells. Increases in cell proliferation may be due to increases in β-catenin protein affecting Wnt signaling, increases in insulin-like growth factor 2 (IGF2) expression, and/or increases in insulin-like growth factor 1 receptor (IGF1R) expression at the protein level. Loss of targeted inhibition of IGF1R by microRNA 675 (miR-675) may be the cause of IGF1R increases, as miR-675 expression is also abrogated with loss of H19 expression in our model. P450 expression patterns were largely unchanged. No change in the production of plasma proteins was found, indicating H19 may not be important for liver maturation despite its role in controlling cell proliferation during liver growth. H19 may be important for normal liver development, and understanding how the liver matures will assist in predicting drug efficacy and toxicity in pediatric populations.
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长期非编码RNA在产后肝脏成熟过程中的发育编程。
影响因子：
3.7
作者：
Peng L;Paulson A;Li H;Piekos S;He X;Li L;Zhong XB
通讯作者：
Zhong XB
影响因子：
3.9
作者：
Cui, Julia Yue;Renaud, Helen J.;Klaassen, Curtis D.
通讯作者：
Klaassen, Curtis D.
DOI：
10.1073/pnas.81.17.5523
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
PACHNIS, V;BELAYEW, A;TILGHMAN, SM
通讯作者：
TILGHMAN, SM
影响因子：
10.5
作者：
Ripoche, MA;Kress, C;Dandolo, L
通讯作者：
Dandolo, L
影响因子：
64.8
作者：
BARTOLOMEI, MS;ZEMEL, S;TILGHMAN, SM
通讯作者：
TILGHMAN, SM