Common pathway signature in lung and liver fibrosis.
Common pathway signature in lung and liver fibrosis.
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DOI：
10.1080/15384101.2016.1152435
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发表时间：
2016-07-02
期刊：
影响因子：
--
通讯作者：
Atala A
中科院分区：
文献类型：
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作者：
Makarev E;Izumchenko E;Aihara F;Wysocki PT;Zhu Q;Buzdin A;Sidransky D;Zhavoronkov A;Atala A
纤维化是一种逐渐积累的细胞外基质成分，包括广泛的不同器官，在世界范围内造成越来越多的发病率和死亡率负担。尽管有巨大的临床影响，但控制纤维化过程的机制尚不清楚，到目前为止，还没有发现临床上可靠的治疗纤维化的方法。在这里，我们应用再生智能，一个新的生物信息学软件套件，利用转录数据定性分析细胞内信号通路激活，评估肺和肝纤维化的分子信号网络。在这两个组织中，我们的分析检测到了与纤维化密切相关的主要保守信号通路，这表明我们的算法识别的一些通路可能是未来研究的有吸引力的目标，但湿实验室尚未证实与纤维化相关。虽然大多数显著中断的通路是组织学上不同的器官特有的，但在肝和肺纤维化样本中，有几条通路同时被激活或下调，这为进化保守的通路提供了新的证据，这些通路可能与可能的治疗靶点相关。虽然未来的验证性研究需要验证这些观察结果，但我们的平台提出了一种很有前途的新方法，用于检测促进纤维化的途径并量身定做正确的治疗方法来防止纤维形成。
Fibrosis, a progressive accumulation of extracellular matrix components, encompasses a wide spectrum of distinct organs, and accounts for an increasing burden of morbidity and mortality worldwide. Despite the tremendous clinical impact, the mechanisms governing the fibrotic process are not yet understood, and to date, no clinically reliable therapies for fibrosis have been discovered. Here we applied Regeneration Intelligence, a new bioinformatics software suite for qualitative analysis of intracellular signaling pathway activation using transcriptomic data, to assess a network of molecular signaling in lung and liver fibrosis. In both tissues, our analysis detected major conserved signaling pathways strongly associated with fibrosis, suggesting that some of the pathways identified by our algorithm but not yet wet-lab validated as fibrogenesis related, may be attractive targets for future research. While the majority of significantly disrupted pathways were specific to histologically distinct organs, several pathways have been concurrently activated or downregulated among the hepatic and pulmonary fibrosis samples, providing new evidence of evolutionary conserved pathways that may be relevant as possible therapeutic targets. While future confirmatory studies are warranted to validate these observations, our platform proposes a promising new approach for detecting fibrosis-promoting pathways and tailoring the right therapy to prevent fibrogenesis.