Activation of Wnt/β-catenin signalling is required for TGF-β/Smad2/3 signalling during myofibroblast proliferation.
Activation of Wnt/β-catenin signalling is required for TGF-β/Smad2/3 signalling during myofibroblast proliferation.
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肌成纤维细胞增殖过程中 TGF-β/Smad2/3 信号传导需要 Wnt/β-连环蛋白信号传导的激活。
DOI：
10.1111/jcmm.13085
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发表时间：
2017-08
影响因子：
5.3
通讯作者：
Gao J
中科院分区：
文献类型：
--
作者：
Xu L;Cui WH;Zhou WC;Li DL;Li LC;Zhao P;Mo XT;Zhang Z;Gao J
动物模型和人类疾病中的纤维化与Wnt/β-连环蛋白通路的异常激活相关。尽管进行了广泛的研究，但仍然没有有效的治疗方法。肌成纤维细胞是主要的效应细胞，负责细胞外基质沉积。抑制肌成纤维细胞的增殖对于治疗纤维化是至关重要的。肌成纤维细胞的增殖可具有导致纤维化的许多触发效应。近年来，Wnt通路已被研究为纤维化疾病的主要贡献者的潜在因素。尽管有这些努力，Wnt介导的促进纤维化反应的具体机制仍然不清楚。转化生长因子-β（TGF-β）和肌成纤维细胞活性在纤维化发病机制中的核心作用已被普遍接受。这两个过程之间相互作用的细节并不明显。本研究旨在评价纤维化标志性蛋白（波形蛋白、α-SMA和胶原I）和TGF-β信号通路（包括smad 2/3及其磷酸化形式p-smad 2/3）的持续表达水平。对β-连环蛋白介导的可能分子机制的详细分析揭示了上皮-间充质转化，并另外证明了成纤维细胞向肌成纤维细胞形式的转化，沿着β-连环蛋白在信号网络调节中的活性增加，其作用是抵消自分泌TGF-β/smad 2/3信号。本研究的一个主要结果是更深入地了解了通过Wnt/β-catenin通过TGFβ1-smad 2/3信号转导激活的上皮和间充质细胞促进肺纤维化的机制。
Fibrosis in animal models and human diseases is associated with aberrant activation of the Wnt/β‐catenin pathway. Despite extensive research efforts, effective therapies are still not available. Myofibroblasts are major effectors, responsible for extracellular matrix deposition. Inhibiting the proliferation of the myofibroblast is crucial for treatment of fibrosis. Proliferation of myofibroblasts can have many triggering effects that result in fibrosis. In recent years, the Wnt pathway has been studied as an underlying factor as a primary contributor to fibrotic diseases. These efforts notwithstanding, the specific mechanisms by which Wnt‐mediated promotes fibrosis reaction remain obscure. The central role of the transforming growth factor‐β (TGF‐β) and myofibroblast activity in the pathogenesis of fibrosis has become generally accepted. The details of interaction between these two processes are not obvious. The present investigation was conducted to evaluate the level of sustained expression of fibrosis iconic proteins (vimentin, α‐SMA and collagen I) and the TGF‐β signalling pathway that include smad2/3 and its phosphorylated form p‐smad2/3. Detailed analysis of the possible molecular mechanisms mediated by β‐catenin revealed epithelial–mesenchymal transition and additionally demonstrated transitions of fibroblasts to myofibroblast cell forms, along with increased activity of β‐catenin in regulation of the signalling network, which acts to counteract autocrine TGF‐β/smad2/3 signalling. A major outcome of this study is improved insight into the mechanisms by which epithelial and mesenchymal cells activated by TGFβ1‐smad2/3 signalling through Wnt/β‐catenin contribute to lung fibrosis.
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影响因子：
5.3
作者：
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