Finding ATF4/p75NTR/IL-8 Signal Pathway in Endothelial-Mesenchymal Transition by Safrole Oxide

文献类型： 外文期刊

第一作者： Ge, Di

作者： Ge, Di;Zhao, Wenbo;Yue, Hongwei;Su, Le;Zhang, ShangLi;Zhao, Jing;Jing, Qingchuan

作者机构：

期刊名称：PLOS ONE （ 影响因子：3.24； 五年影响因子：3.788 ）

ISSN： 1932-6203

年卷期： 2014 年 9 卷 6 期

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收录情况： SCI

摘要： Targeting the endothelial-to-mesenchymal transition Endo T) may be a novel therapeutic strategy for cancer and various diseases induced by fibrosis. We aimed to den small chemical molecule as an inducer of EndoMT and find a new signal pathway by using the inducer. Safrole oxide (SFO) 50 mu g/ml, could most effectively induce EndoMT within 12 h. To understand the underlying molecular mechanism, we performed microarray, quantitative real-time PCR and western blot analysis to find key factors involved in SFO-induced EndoMT and demonstrated the involvement of the factors by RNAi. The expression of activating transcription factor 4 (ATF4), p75 neurotrophin receptor (p75NTR), and interleukin 8 (IL-8) was greatly increased in SFO-induced EndoMT. Knockdown of ATF4 inhibited the SFO-induced EndoMT completely, and knockdown of p75NTR or 1L-8 partially inhibited the EnoMT, which suggests that all three factors were involved in the process. Furthermore knockdown of p75NTR inhibited the SFO-increased IL-8 expression and secretion and knockdown of ATF4 inhibited SFO-increased p75NTR level significantly. The ATF4/p75NTR/1L-8 signal pathway may have an important role in EndoMT induced by SFO. Our findings support potential novel targets for the therapeutics of cancer and fibrosis disease.

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