Sun Kai, Battle Michele A, Misra Ravi P, Duncan Stephen A
Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Hepatology. 2009 May;49(5):1645-54. doi: 10.1002/hep.22834.
Serum response factor (SRF) is a transcription factor that binds to a CarG box motif within the serum response element of genes that are expressed in response to mitogens. SRF plays essential roles in muscle and nervous system development; however, little is known about the role of SRF during liver growth and function. To examine the function of SRF in the liver, we generated mice in which the Srf gene was specifically disrupted in hepatocytes. The survival of mice lacking hepatic SRF activity was lower than that of control mice; moreover, surviving mutant mice had lower blood glucose and triglyceride levels compared with control mice. In addition, Srf(loxP/loxP)AlfpCre mice were smaller and had severely depressed levels of serum insulin-like growth factor 1 (IGF-1). Srf-deficient livers were also smaller than control livers, and liver cell proliferation and viability were compromised. Gene array analysis of SRF depleted livers revealed a reduction in many messenger RNAs, including those encoding components of the growth hormone/IGF-1 pathway, cyclins, several metabolic regulators, and cytochrome p450 enzymes.
SRF is essential for hepatocyte proliferation and survival, liver function, and control of postnatal body growth by regulating hepatocyte gene expression.
血清反应因子（SRF）是一种转录因子，可与因有丝分裂原刺激而表达的基因的血清反应元件内的CArG框基序结合。SRF在肌肉和神经系统发育中起重要作用；然而，关于SRF在肝脏生长和功能中的作用知之甚少。为了研究SRF在肝脏中的功能，我们构建了肝细胞中Srf基因特异性缺失的小鼠。缺乏肝脏SRF活性的小鼠的存活率低于对照小鼠；此外，存活的突变小鼠与对照小鼠相比，血糖和甘油三酯水平较低。此外，Srf(loxP/loxP)AlfpCre小鼠体型较小，血清胰岛素样生长因子1（IGF-1）水平严重降低。Srf基因缺陷的肝脏也比对照肝脏小，肝细胞增殖和活力受损。对SRF缺失肝脏的基因阵列分析显示，许多信使RNA减少，包括那些编码生长激素/IGF-1途径成分、细胞周期蛋白、几种代谢调节因子和细胞色素P450酶的信使RNA。
SRF通过调节肝细胞基因表达，对肝细胞增殖和存活、肝功能以及出生后身体生长的控制至关重要。
