Department of Biochemistry and Molecular Biology, UT-Houston Graduate School of Biomedical Sciences, UT MD Anderson Cancer Center, Houston, TX 77030, USA.
Int J Biochem Cell Biol. 2011 Feb;43(2):189-97. doi: 10.1016/j.biocel.2010.03.013. Epub 2010 Mar 20.
An increasing demand for new strategies in cancer prevention and regenerative medicine requires a better understanding of molecular mechanisms that control cell proliferation in tissue-specific manner. Regenerating liver is a unique model allowing use of biochemical, genetic, and engineering tools to uncover molecular mechanisms and improve treatment of hepatic cancers, liver failure, and fibrotic disease. Molecular mechanisms of liver regeneration involve extra- and intracellular factors to activate transcription of genes normally silenced in quiescent liver. While many upstream signaling pathways of the regenerating liver have been extensively studied, our knowledge of the downstream effectors, transcription factors (TFs), remains limited. This review describes consecutive engagement of pre-existing and de novo synthesized TFs, as cascades that regulate expression of growth-related and metabolic genes during liver regeneration after partial hepatectomy in mice. Several previously recognized regulators of regenerating liver are described in the light of recently identified co-activator and co-repressor complexes that interact with primary DNA-binding TFs. Published results of gene expression and chromatin immunoprecipitation analyses, as well as studies of transgenic mouse models, are used to emphasize new potential regulators of transcription during liver regeneration. Finally, a more detailed description of newly identified transcriptional regulators of liver regeneration illustrates the tightly regulated balance of proliferative and metabolic responses to partial hepatectomy.
癌症预防和再生医学对新策略的需求不断增加，这就需要更好地了解控制组织特异性细胞增殖的分子机制。再生肝脏是一种独特的模型，它可以利用生化、遗传和工程工具来揭示分子机制，并改善对肝癌、肝衰竭和纤维化疾病的治疗。肝脏再生的分子机制涉及细胞外和细胞内因素，以激活在静止肝脏中被沉默的基因的转录。虽然再生肝脏的许多上游信号通路已经得到了广泛的研究，但我们对下游效应物（转录因子）的了解仍然有限。本综述描述了在小鼠部分肝切除后肝脏再生过程中，预存和新合成的转录因子作为级联反应，依次激活与生长相关和代谢基因的表达。本文根据最近发现的与主要 DNA 结合转录因子相互作用的共激活和共抑制复合物，重新描述了已知的再生肝脏调控因子。利用已发表的基因表达和染色质免疫沉淀分析结果以及转基因小鼠模型的研究结果，强调了在肝脏再生过程中，转录的新潜在调控因子。最后，对新发现的肝脏再生转录调控因子的更详细描述说明了部分肝切除后增殖和代谢反应的严格调控平衡。
