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题目:: Neuron-derived orphan receptor 1 promotes proliferation of quiescent hepatocytes.
作者:: Vacca(Michele),Murzilli(Stefania),Salvatore(Lorena),Di Tullio(Giuseppe),D'Orazio(Andria),Lo Sasso(Giuseppe),Graziano(Giusi),Pinzani(Massimo),Chieppa(Marcello),Mariani-Costantini(Renato),Palasciano(Giuseppe),Moschetta(Antonio)
状态:: 发布时间2013-05-28 , 更新时间 2013-05-28
期刊:: Gastroenterology
摘要:: Studies of the transcriptional networks that regulate nuclear receptor-mediated proliferation of quiescent hepatocytes could lead to new information about liver growth and hepatoprotective strategies.,We used quantitative real-time PCR to analyze expression of neuron-derived orphan receptor 1 (Nor-1) and its target genes during liver regeneration after hepatectomy in mice, and in hepatocellular carcinoma (HCC) samples from patients. We used adenoviral vectors to express Nor-1 in normal liver (Ad/CMV/V5-Nor-1), or reduce its level with small hairpin RNAs (Ad/BLOCK-iT/Nor-1(small hairpin RNA)) after partial hepatectomy.,Levels of Nor-1 messenger RNA and protein, and transcription of Nor-1 target genes (Ccnd1 and Vcam-1), increased during the late priming and proliferative phases of liver regeneration after partial hepatectomy. Levels of NOR-1 messenger RNA and transcription of its target gene CCND1 and of the NOR-1 subfamily member NUR-77 also increased in human HCC samples compared with paired HCC-free tissue. Ad-Nor-1(small hairpin RNA) reduced the hepatocyte proliferation after hepatectomy. Overexpression of Nor-1 in normal livers of mice induced proliferation of quiescent hepatocytes independently of interleukin-6 and tumor necrosis factor-α signaling. In gene expression profile analysis, Nor-1 altered expression of genes involved in the cell cycle, proliferation, and tumorigenesis.,In mice, the orphan nuclear receptor Nor-1 activates proliferation of quiescent hepatocytes and is required for hepatocyte proliferation after partial hepatectomy. Nor-1 and its gene targets are also up-regulated in human HCC samples. Nor-1 activates a transcriptional program that induces hepatocyte proliferation independently of inflammatory signaling pathways.
语言:: eng
DOI:: 10.1053/j.gastro.2013.02.027

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