Extending the time window of mammalian heart regeneration by thymosin beta 4.
Extending the time window of mammalian heart regeneration by thymosin beta 4.
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胸腺肽 β 4 延长哺乳动物心脏再生的时间窗。
DOI：
10.1111/jcmm.12421
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发表时间：
2014-12
影响因子：
5.3
通讯作者：
Shengshou H
中科院分区：
文献类型：
--
作者：
Rui L;Yu N;Hong L;Feng H;Chunyong H;Jian M;Zhe Z;Shengshou H
最近的研究表明，1日龄新生小鼠的心脏可以再生，部分手术切除后Wt1+ EPDCs迁移到心肌区域，但这种能力在7日龄时丧失。通过Tβ4维持Wt1的表达和EPDCs的迁移特性，探讨其恢复小鼠心脏再生能力的可能性。每天腹腔注射1日龄小鼠Tβ4，7天后行根尖切除术。切除后21天，形态学分析显示，Tβ4处理组小鼠切除的心室心尖再生，而PBS对照组小鼠出现明显的纤维化，无心尖再生。与对照组相比，Tβ4治疗组小鼠的心室射血分数和短轴缩短率显著改善。在再生过程中，Wt1+ EPDCs向心肌区迁移，部分表达Islet 1和成熟心肌细胞标志物cTnT、SαA。Wt1+ EPDCs的这些特征也见于出生后1天进行心尖切除的小鼠的心脏再生中。Tβ4对细胞周期活性无本质影响，因为在Tβ4处理的心脏中未观察到肌动蛋白丝的破坏。提示Tβ4可使新生小鼠心脏再生潜能延长至生后第7天，Wt1+ EPDCs动员可能在此延长过程中起重要作用。
Recent studies demonstrated that the heart of 1-day-old neonatal mice could regenerate, with Wt1+ EPDCs migrating into myocardial regions after partial surgical resection, but this capacity was lost by 7 days of age. By treatment with Tβ4 to maintain Wt1 expression and retain the migrating feature of EPDCs in neonatal mice, we explored the possibility of restoring the cardiac regeneration potential of mice. We intraperitoneally injected Tβ4 into 1-day-old mice on daily basis and then apical resection was performed on the mice 7 days later. Twenty one days after the resection, morphological analysis revealed that the Tβ4-treated mice regenerated the resected ventricular apex, while the mice in PBS control group developed significant fibrosis without apical regeneration. The Tβ4-treated mice had significantly better ventricular ejection fraction and fractional shortening than controls. During the process of regeneration, Wt1+ EPDCs migrated into myocardial region and some of them expressed Islet1 and the markers for mature cardiomyocytes, such as cTnT and SαA. These characteristics of Wt1+ EPDCs were also seen in the heart regeneration of mice subjected to apical resection 1 day after birth. Tβ4 has no essential effect on cell cycle activity as no disruption of actin filaments was observed in Tβ4-treated hearts. These results revealed that the cardiac regeneration potential of neonatal mice could be extended to the 7th post-natal day by Tβ4 and Wt1+ EPDCs mobilization might play an important role in the extension.
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影响因子：
64.8
作者：
Qian, Li;Huang, Yu;Srivastava, Deepak
通讯作者：
Srivastava, Deepak
影响因子：
5.3
作者：
Manole CG;Cismaşiu V;Gherghiceanu M;Popescu LM
通讯作者：
Popescu LM
影响因子：
64.8
作者：
Laugwitz, KL;Moretti, A;Chien, KR
通讯作者：
Chien, KR
影响因子：
5.3
作者：
Popescu LM;Manole CG;Gherghiceanu M;Ardelean A;Nicolescu MI;Hinescu ME;Kostin S
通讯作者：
Kostin S
影响因子：
64.8
作者：
Zhou, Bin;Ma, Qing;Pu, William T.
通讯作者：
Pu, William T.