Restoration of liver mass after injury requires proliferative and not embryonic transcriptional patterns
Restoration of liver mass after injury requires proliferative and not embryonic transcriptional patterns
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DOI：
10.1074/jbc.m608441200
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发表时间：
2007-04-13
影响因子：
4.8
通讯作者：
Karp, Seth J.
中科院分区：
文献类型：
--
作者：
Otu, Hasan H.;Naxerova, Kamila;Karp, Seth J.
正常成人肝脏在损伤后具有独特的更新和修复能力。这种反应是否代表各种肝脏成分的简单增生或需要发育中肝脏遗传程序的重演尚不清楚。为了研究这些可能性，我们检查了部分肝切除术后成人肝脏的转录程序，并将其与发育中的胚胎肝脏进行了对比。主成分分析表明，在肝再生过程中的基因表达的时间序列不分离根据发展转录模式。基因本体分析显示，肝切除术后的肝脏恢复和肝脏发育在转录因子和染色质结构修饰方面存在显着差异。相反，组织在增殖相关基因方面是相似的。与这些发现一致，实时聚合酶链反应显示，已知在肝脏发育中重要的转录因子在肝脏再生过程中不会被诱导。这三条证据表明，在转录水平上，损伤后肝脏质量的恢复最好描述为肝细胞增生，而不是真正的再生。我们推测这种新的基因表达模式可能是肝脏在损伤后自我修复的独特能力的基础。
Normal adult liver is uniquely capable of renewal and repair after injury. Whether this response represents simple hyperplasia of various liver elements or requires recapitulation of the genetic program of the developing liver is not known. To study these possibilities, we examined transcriptional programs of adult liver after partial hepatectomy and contrasted these with developing embryonic liver. Principal component analysis demonstrated that the time series of gene expression during liver regeneration does not segregate according to developmental transcription patterns. Gene ontology analysis revealed that liver restoration after hepatectomy and liver development differ dramatically with regard to transcription factors and chromatin structure modification. In contrast, the tissues are similar with regard to proliferation-associated genes. Consistent with these findings, real-time polymerase chain reaction showed transcription factors known to be important in liver development are not induced during liver regeneration. These three lines of evidence suggest that at a transcriptional level restoration of liver mass after injury is best described as hepatocyte hyperplasia and not true regeneration. We speculate this novel pattern of gene expression may underlie the unique capacity of the liver to repair itself after injury.