To reveal pharmacological targets and molecular mechanisms of curcumol against interstitial cystitis
To reveal pharmacological targets and molecular mechanisms of curcumol against interstitial cystitis
复制标题
揭示姜黄酚抗间质性膀胱炎的药理靶点及分子机制
DOI：
10.1016/j.jare.2019.05.003
复制
发表时间：
2019-11-01
影响因子：
10.7
通讯作者：
Su, Min
中科院分区：
文献类型：
--
作者：
Wu, Ka;Wei, Pingyuan;Su, Min
本研究旨在揭示姜黄酚对抗间质性膀胱炎（IC）的预测靶点和生物学机制。通过利用现有的数据库和生物信息学分析，分别确定了IC的致病靶点和姜黄酚的功能靶点。在筛选姜黄酚对抗IC的主要预测靶点、生物过程和信号通路之前，建立了功能性蛋白质-蛋白质相互作用（PPI）网络。在生物信息学研究中，独创性通路分析（IPA）数据表明姜黄醇通过调节多管信号通路（包括酪氨酸蛋白激酶2（PTK2）通路）发挥抗IC功效。进一步通过差异表达分析收获了姜黄酚针对IC的最佳18个生物靶点。其中受体酪氨酸蛋白激酶erbB-2（ERBB2）、表皮生长因子受体（EGFR）和PTK2是最重要的预测靶点。在进一步验证的实验中，代表性地选择PTK2和磷酸化PTK2（p-PTK2）进行人类和动物IC样品的测试。结果，在人IC切片中观察到肿瘤坏死因子α（TNF-α）、PTK2和p-PTK2（Tyr397）的免疫反应蛋白增加，并伴随尿液参数的改变。有趣的是，姜黄酚治疗的IC小鼠显示膀胱样本中PTK2、p-PTK2(Tyr397)的细胞内表达减少，同时血液中白细胞介素6(IL-6)、TNF-α的炎症细胞因子降低。总之，目前的生物信息学数据和初步研究结果表明，姜黄酚对抗IC的主要靶点可能是筛选和治疗IC的潜在生物标志物，例如PTK2分子。 (C) 2019 年作者。由 Elsevier B.V. 代表开罗大学出版。
This study was designed to reveal the predictive targets and biological mechanisms of curcumol against interstitial cystitis (IC). By use of available databases and bioinformatic assays, pathogenetic targets of IC and functional targets of curcumol were identified respectively. A network of functional protein-protein interaction (PPI) was produced before screening the main predictive targets, biological processes and signaling pathways of curcumol against IC. In bioinformatic findings, the data of ingenuity pathway analysis (IPA) delineated that curcumol exerted anti-IC benefits through regulating multipronged signaling pathways, including tyrosine protein kinase-2 (PTK2) pathway. Further, optimal 18 biotargets of curcumol against IC were harvested through differential expression analysis. And the predictive targets of receptor tyrosine-protein kinase erbB-2 (ERBB2), epidermal growth factor receptor (EGFR) and PTK2 were the most important molecules. In further validated experiments, PTK2 and phosphorylation PTK2 (p-PTK2) were representatively selected for testing by human and animal IC samples. As results, increased immunoreactive proteins of tumor necrosis factor alpha (TNF-alpha), PTK2 and p-PTK2(Tyr397) in human IC sections were observed, accompanied with altered urinary parameters. Interestingly, curcumol-treated IC mice showed that intracellular expressions of PTK2, p-PTK2(Tyr397) in bladder samples were reduced, accompanied with lowered blood inflammatory cytokines of interleukin 6 (IL-6), TNF-alpha. In conclusion, the current bioinformatic data and preliminary findings unravel that the predominant targets of curcumol against IC may be the potential biological markers for screening and treating IC, such as PTK2 molecule. (C) 2019 The Authors. Published by Elsevier B.V. on behalf of Cairo University.