Acute inflammation stimulates a regenerative response in the neonatal mouse heart.
Acute inflammation stimulates a regenerative response in the neonatal mouse heart.
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急性炎症刺激新生小鼠心脏的再生反应
DOI：
10.1038/cr.2015.110
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发表时间：
2015-10
期刊：
影响因子：
44.1
通讯作者：
Hu S
中科院分区：
文献类型：
--
作者：
Han C;Nie Y;Lian H;Liu R;He F;Huang H;Hu S
新生1日龄小鼠的心脏损伤刺激了以反应性心肌细胞增殖为特征的再生反应，这与成年小鼠的纤维化修复过程不同。急性炎症在心脏损伤后立即发生，通常被认为通过促进成人瘢痕形成而对心脏再生产生负面影响；然而，对于急性炎症在新生小鼠心脏再生反应中的作用，人们知之甚少。在这里，我们展示了在新生小鼠心脏顶端心肌内微量注射免疫原酵母多糖A颗粒后，急性炎症诱导了心肌细胞的增殖。我们还发现，新生小鼠心脏损伤诱导的再生反应在免疫抑制后暂停，并且在缺乏白细胞介素6(IL-6)的情况下，心肌细胞不能在新生心脏损伤后重新激活增殖。此外，心肌细胞特异性缺失信号转导和转录激活子3(STAT3)是IL-6信号的主要下游效应因子，可减少心尖切除术后心肌细胞的反应性增殖。我们的结果表明，急性炎症刺激了新生小鼠心脏的再生反应，提示炎症信号的调节可能在心脏再生医学中具有重要意义。
Cardiac injury in neonatal 1-day-old mice stimulates a regenerative response characterized by reactive cardiomyocyte proliferation, which is distinguished from the fibrotic repair process in adults. Acute inflammation occurs immediately after heart injury and has generally been believed to exert a negative effect on heart regeneration by promoting scar formation in adults; however, little is known about the role of acute inflammation in the cardiac regenerative response in neonatal mice. Here, we show that acute inflammation induced cardiomyocyte proliferation after apical intramyocardial microinjection of immunogenic zymosan A particles into the neonatal mouse heart. We also found that cardiac injury-induced regenerative response was suspended after immunosuppression in neonatal mice, and that cardiomyocytes could not be reactivated to proliferate after neonatal heart injury in the absence of interleukin-6 (IL-6). Furthermore, cardiomyocyte-specific deletion of signal transducer and activator of transcription 3 (STAT3), the major downstream effector of IL-6 signaling, decreased reactive cardiomyocyte proliferation after apical resection. Our results indicate that acute inflammation stimulates the regenerative response in neonatal mouse heart, and suggest that modulation of inflammatory signals might have important implications in cardiac regenerative medicine.