Peng Lai, Piekos Stephanie C, Guo Grace L, Zhong Xiao-Bo
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA.
Department of Pharmacology and Toxicology, School of Pharmacy, Rutgers University, Piscataway, NJ 08807, USA.
Nucl Receptor Res. 2017;4. doi: 10.11131/2017/101308. Epub 2017 Oct 20.
The liver is a vital organ with critical functions in metabolism of various biologically useful materials, synthesis of several vital proteins, detoxification of toxic substances, and immune defense. Most liver functions are not mature at birth and many changes happen during postnatal liver development, which lead to differential vulnerabilities of the liver at different developmental stages. However, the details of what changes occur in liver after birth, at what developmental stages they occur, and molecular mechanisms in the regulation of the developmental process are not clearly known. The nuclear receptor Farnesoid X receptor (FXR) is an important transcriptional regulator in liver. Here, we used RNA-Sequencing to analyze the transcriptome of mouse liver from perinatal to adult ages in both C57BL/6 and mice. We have defined a clear timeline of functional transition from prenatal through neonatal and adolescent to adult in C57BL/6 mice. Without FXR, activation of neonatal-specific pathways was prolonged and maturation of multiple metabolic pathways was delayed. The loss of FXR also led to increased expression of 27 other transcription regulators. Our data support a conclusion that developmental transcriptome revealed significant functional transition during postnatal liver development and FXR plays an important role in control of postnatal liver maturation.
肝脏是一个重要器官，在各种生物有用物质的代谢、多种重要蛋白质的合成、有毒物质的解毒以及免疫防御方面具有关键功能。大多数肝脏功能在出生时并不成熟，在出生后肝脏发育过程中会发生许多变化，这导致肝脏在不同发育阶段具有不同的易损性。然而，出生后肝脏发生了哪些变化、这些变化发生在哪些发育阶段以及发育过程调控中的分子机制尚不清楚。核受体法尼酯X受体（FXR）是肝脏中一种重要的转录调节因子。在此，我们使用RNA测序分析了C57BL/6小鼠和[此处原文缺失相关小鼠信息]从围产期到成年期的肝脏转录组。我们已经明确了C57BL/6小鼠从产前到新生儿期、青少年期再到成年期功能转变的清晰时间线。没有FXR时，新生儿特异性途径的激活会延长，多种代谢途径的成熟会延迟。FXR的缺失还导致另外27种转录调节因子的表达增加。我们的数据支持这样一个结论，即发育转录组揭示了出生后肝脏发育过程中的显著功能转变，并且FXR在控制出生后肝脏成熟中起重要作用。
