Canonical Wnt/β-catenin signaling in epicardial fibrosis of failed pediatric heart allografts with diastolic dysfunction.
Canonical Wnt/β-catenin signaling in epicardial fibrosis of failed pediatric heart allografts with diastolic dysfunction.
复制标题
伴有舒张功能障碍的失败儿科同种异体心脏移植物心外膜纤维化中的典型 Wnt/β-连环蛋白信号传导。
DOI：
10.1016/j.carpath.2012.03.004
复制
发表时间：
2013-01
影响因子：
3.7
通讯作者：
Li, Faqian
中科院分区：
文献类型：
--
作者：
Ye, Bo;Ge, Yao;Perens, Gregory;Hong, Longsheng;Xu, Haodong;Fishbein, Michael C.;Li, Faqian
关键词：
舒张功能障碍的小儿心脏移植失败表现为严重的心外膜纤维化。这一过程的分子机制知之甚少。经典Wnt/β-catenin信号传导在上皮-间充质转化中起重要作用，并与纤维化疾病有关。在这项研究中，我们检验了经典Wnt/β-catenin信号在终末期功能障碍的小儿同种异体移植物的心外膜纤维化中被激活的假设。对12例14次心脏移植患者的14个移植心脏进行β-catenin及其核结合伙伴T细胞因子/淋巴增强因子（TCF/LEF）家族转录因子的免疫组织化学染色。14个年龄匹配的自体心脏，来自接受首次心脏移植但无心外膜纤维化证据的患者，用作对照。移植物中的心外膜成纤维细胞显示β-连环蛋白的核积聚。这些细胞还显示TCF-4的核阳性。心外膜无TCF-3表达。TCF-1和LEF-1在淋巴细胞中被观察到，但在心外膜的其他类型的细胞中未观察到。这些发现表明经典Wnt/β-连环蛋白信号传导与小儿心脏移植失败的心外膜纤维化之间存在关联。如果这一通路的激活被证明是心外膜纤维化的原因，那么抑制这一通路可能有助于防止这种破坏性的过程。
Failed pediatric heart allografts with diastolic dysfunction exhibit severe epicardial fibrosis. The molecular mechanism underlying this process is poorly understood. Canonical Wnt/β-catenin signaling plays an important role in epithelial-mesenchymal transition and is implicated in fibrosing diseases. In this study, we tested the hypothesis that canonical Wnt/β-catenin signaling is activated in epicardial fibrosis of end-stage dysfunctional pediatric allografts. Fourteen explanted heart grafts of 12 patients who had undergone 14 heart transplantations were used for immunohistochemical staining of β-catenin and its nuclear binding partners, T-cell factor/lymphoid enhancer factor (TCF/LEF) family transcriptional factors. Fourteen age-matched native hearts from patients who undergone first heart transplantation without evidence of epicardial fibrosis were used as controls. Epicardial fibroblasts from explanted allografts demonstrated nuclear accumulation of β-catenin. These cells also showed nuclear positivity for TCF-4. No TCF-3 expression was present in the epicardium. TCF-1 and LEF-1 were observed in lymphocytes, but not in other cell types of the epicardium. These findings suggest an association between canonical Wnt/beta-catenin signaling and epicardial fibrosis of failed pediatric heart allografts. Should activation of this pathway be shown to be causal to epicardial fibrosis in this setting, then inhibition of this pathway may help to prevent this devastating process.
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DOI：
10.1073/pnas.102657399
发表时间：
2002-05-14
影响因子：
11.1
作者：
Cheon, SS;Cheah, AYL;Alman, BA
通讯作者：
Alman, BA
影响因子：
4.8
作者：
Kishida, S;Yamamoto, H;Kikuchi, A
通讯作者：
Kikuchi, A
影响因子：
8.9
作者：
Stewart, S;Winters, GL;Billingham, ME
通讯作者：
Billingham, ME
影响因子：
8.9
作者：
Pahl, E;Naftel, DC;Kirklin, J
通讯作者：
Kirklin, J
影响因子：
20.3
作者：
CASTROP, J;VANWICHEN, D;CLEVERS, H
通讯作者：
CLEVERS, H