The TrkB-T1 receptor mediates BDNF-induced migration of aged cardiac microvascular endothelial cells by recruiting Willin
The TrkB-T1 receptor mediates BDNF-induced migration of aged cardiac microvascular endothelial cells by recruiting Willin
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TrkB-T1 受体通过募集 Willin 介导 BDNF 诱导的衰老心脏微血管内皮细胞迁移
DOI：
10.1111/acel.12881
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发表时间：
2019
期刊：
影响因子：
7.8
通讯作者：
Cai Dongqing
中科院分区：
文献类型：
--
作者：
Wang Zhefeng;Chen Yilin;Chen Xuwei;Zheng Xin;Xu Ganlin;Yuan Ziqiang;Zhao Hui;Chen Wensheng;Li Lilin;Zheng Nianjue;Shen Xiaotao;Li Yanmei;Qi Xufeng;Cai Dongqing
年龄相关的心肌血管生成潜力下降的机制尚未完全了解。我们之前的报道显示，心脏微血管内皮细胞（CMECs）的衰老导致其受体Trk亚型表达的变化：在三种亚型（TrkB‐FL，TrkB‐T1和TrkB‐T2）中，只有截短的TrkB‐T1亚型在衰老的CMECs中继续表达，这导致CMECs在衰老心脏中的迁移减少。到目前为止，BDNF如何通过老年CMECs中截短的TrkB-T1亚型诱导信号传导仍不清楚。在这里，我们首先证明了衰老的CMECs利用BDNF-TrkB-T1信号转导来招募Willin作为下游效应子，以进一步激活Hippo通路，然后促进迁移。这些发现表明，衰老过程通过BDNF-TrkB-T1-Willin-Hippo通路转导BDNF信号，改变了表达TrkB-T1受体的老年CMEC的表型，这种变化可能是老年心脏中观察到的功能障碍性心脏血管生成的重要机制和治疗靶点。
The mechanism of age‐related decline in the angiogenic potential of the myocardium is not yet fully understood. Our previous report revealed that the aging of cardiac microvascular endothelial cells (CMECs) led to changes in their expression of receptor Trk isoforms: among the three isoforms (TrkB‐FL, TrkB‐T1 and TrkB‐T2), only the truncated TrkB‐T1 isoform continued to be expressed in aged CMECs, which led to decreased migration of CMECs in aging hearts. Thus far, how BDNF induces signalling through the truncated TrkB‐T1 isoform in aged CMECs remains unclear. Here, we first demonstrated that aged CMECs utilize BDNF–TrkB‐T1 signalling to recruit Willin as a downstream effector to further activate the Hippo pathway, which then promotes migration. These findings suggest that the aging process shifts the phenotype of aged CMECs that express TrkB‐T1 receptors by transducing BDNF signals via the BDNF–TrkB‐T1–Willin–Hippo pathway and that this change might be an important mechanism and therapeutic target of the dysfunctional cardiac angiogenesis observed in aged hearts.