S100A8/MYD88/NF-O⟩B: a novel pathway involved in cardiomyocyte hypertrophy driven by thyroid hormone
S100A8/MYD88/NF-O⟩B: a novel pathway involved in cardiomyocyte hypertrophy driven by thyroid hormone
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DOI：
10.1007/s00109-017-1511-y
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发表时间：
2017-06-01
影响因子：
4.7
通讯作者：
Morais Barreto-Chaves, Maria Luiza
中科院分区：
文献类型：
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作者：
Cremasco Takano, Ana Paula;Munhoz, Carolina Demarchi;Morais Barreto-Chaves, Maria Luiza
最近的研究证明，炎症相关途径参与了心脏肥大的发展和对心血管系统的其他后果，包括钙结合蛋白S100 A8。然而，这从来没有被调查在甲状腺激素（TH）引起的心肌肥大。因此，我们的目的是测试是否S100 A8和相关的信号分子，髓样分化因子-88（MyD 88）和核因子κ B（NF-κ B B），可以与TH诱导的心肌细胞肥大。我们的结果表明，在TH刺激后，S100 A8/MyD 88/NF-κ B信号通路在心肌细胞中被激活。S100 A8和MyD 88的敲低表明这些分子响应于TH对心肌细胞肥大的贡献，如通过细胞表面积、亮氨酸掺入测定和基因表达所评估的。此外，S100 A8和MyD 88是NF-κ B B活化的关键介质，NF-κ B活化也参与TH处理的心肌细胞的肥大生长。通过使用心肌细胞特异性抑制NF-κ B的转基因小鼠，在体内证实了NF-κ B对TH诱导的心脏肥大的贡献，这支持了体外数据。这些数据确定了一个新的途径调节TH介导的心肌细胞肥大。然而，这一新途径在TH的短期和长期心脏效应中的潜在作用仍有待进一步研究。
Recent studies have evidenced the involvement of inflammation-related pathways to the development of cardiac hypertrophy and other consequences on the cardiovascular system, including the calcium-binding protein S100A8. However, this has never been investigated in the thyroid hormone (TH)-prompted cardiac hypertrophy. Thus, we aimed to test whether S100A8 and related signaling molecules, myeloid differentiation factor-88 (MyD88) and nuclear factor kappa B (NF-kappa B), could be associated with the cardiomyocyte hypertrophy induced by TH. Our results demonstrate that the S100A8/MyD88/NF-kappa B signaling pathway is activated in cardiomyocytes following TH stimulation. The knockdown of S100A8 and MyD88 indicates the contribution of those molecules to cardiomyocyte hypertrophy in response to TH, as evaluated by cell surface area, leucine incorporation assay, and gene expression. Furthermore, S100A8 and MyD88 are crucial mediators of NF-kappa B activation, which is also involved in the hypertrophic growth of TH-treated cardiomyocytes. Supporting the in vitro data, the contribution of NF-kappa B for TH-induced cardiac hypertrophy is confirmed in vivo, by using transgenic mice with cardiomyocyte-specific suppression of NF-kappa B. These data identify a novel pathway regulated by TH that mediates cardiomyocyte hypertrophy. However, the potential role of this new pathway in short and long-term cardiac effects of TH remains to be further investigated.