Parsing the roles of the transcription factors GATA-4 and GATA-6 in the adult cardiac hypertrophic response.
Parsing the roles of the transcription factors GATA-4 and GATA-6 in the adult cardiac hypertrophic response.
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DOI：
10.1371/journal.pone.0084591
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Molkentin JD
中科院分区：
文献类型：
--
作者：
van Berlo JH;Aronow BJ;Molkentin JD
编程心脏肥大的转录密码涉及含锌指的DNA结合因子加塔-4和加塔-6，这两者都是引起成人心脏肥大反应所必需的。在这里，我们在小鼠心脏中进行了Gata 4或Gata 6的条件性基因缺失，并在心脏中使用编码加塔-4或加塔-6的转基因进行了相互基因替换，作为分析加塔-4和加塔-6与独特功能作用的剂量效应的手段。我们确定加塔-4和加塔-6在压力超负荷刺激后心脏的肥大性生长反应编程中发挥冗余和剂量敏感的作用。然而，在允许心脏在压力过载刺激后补偿和抵抗心力衰竭中鉴定了非冗余功能，因为Gata 4和Gata 6缺失都不能通过相互转基因的表达完全挽救。例如，只有Gata 4心脏特异性缺失阻断了对压力过载刺激的新血管生成反应。这些基因缺失小鼠心脏的基因表达谱显示了重叠和独特的转录密码，这是目前。这些结果表明，加塔-4和加塔-6在编程心脏肥大中发挥剂量依赖性和冗余作用，但每一个在维持心脏稳态和抵抗损伤后的心力衰竭中具有更复杂的作用，不能被另一个补偿。
The transcriptional code that programs cardiac hypertrophy involves the zinc finger-containing DNA binding factors GATA-4 and GATA-6, both of which are required to mount a hypertrophic response of the adult heart. Here we performed conditional gene deletion of Gata4 or Gata6 in the mouse heart in conjunction with reciprocal gene replacement using a transgene encoding either GATA-4 or GATA-6 in the heart as a means of parsing dosage effects of GATA-4 and GATA-6 versus unique functional roles. We determined that GATA-4 and GATA-6 play a redundant and dosage-sensitive role in programming the hypertrophic growth response of the heart following pressure overload stimulation. However, non-redundant functions were identified in allowing the heart to compensate and resist heart failure after pressure overload stimulation, as neither Gata4 nor Gata6 deletion was fully rescued by expression of the reciprocal transgene. For example, only Gata4 heart-specific deletion blocked the neoangiogenic response to pressure overload stimulation. Gene expression profiling from hearts of these gene-deleted mice showed both overlapping and unique transcriptional codes, which is presented. These results indicate that GATA-4 and GATA-6 play a dosage-dependent and redundant role in programming cardiac hypertrophy, but that each has a more complex role in maintaining cardiac homeostasis and resistance to heart failure following injury that cannot be compensated by the other.
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影响因子：
20.1
作者：
Oka, T;Maillet, M;Molkentin, JD
通讯作者：
Molkentin, JD
影响因子：
4.8
作者：
Liang, QR;De Windt, LJ;Molkentin, JD
通讯作者：
Molkentin, JD
DOI：
10.1073/pnas.1104499108
发表时间：
2011-07-26
影响因子：
11.1
作者：
van Berlo, Jop H.;Elrod, John W.;Molkentin, Jeffery D.
通讯作者：
Molkentin, Jeffery D.
DOI：
10.1073/pnas.0604604103
发表时间：
2006-07-25
影响因子：
11.1
作者：
Xin, Mei;Davis, Christopher A.;Olson, Eric N.
通讯作者：
Olson, Eric N.
影响因子：
2.7
作者：
Zhao, Roong;Watt, Alistair J.;Duncan, Stephen A.
通讯作者：
Duncan, Stephen A.