To reveal pharmacological targets and molecular mechanisms of curcumol against interstitial cystitis

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 function...

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Main Authors: Ka Wu, Pingyuan Wei, Meizhen Liu, Xiaoliu Liang, Min Su
Format: Article
Language:English
Published: Elsevier 2019-11-01
Series:Journal of Advanced Research
Online Access:http://www.sciencedirect.com/science/article/pii/S2090123219300918
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author Ka Wu
Pingyuan Wei
Meizhen Liu
Xiaoliu Liang
Min Su
author_facet Ka Wu
Pingyuan Wei
Meizhen Liu
Xiaoliu Liang
Min Su
author_sort Ka Wu
collection DOAJ
description 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-α), PTK2 and p-PTK2Tyr397 in human IC sections were observed, accompanied with altered urinary parameters. Interestingly, curcumol-treated IC mice showed that intracellular expressions of PTK2, p-PTK2Tyr397 in bladder samples were reduced, accompanied with lowered blood inflammatory cytokines of interleukin 6 (IL-6), TNF-α. 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. Keywords: Curcumol, Interstitial cystitis, Bioinformatics, Biomarkers, PTK2, protein-protein interaction
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spelling doaj.art-277d9eaacc1b4f17a4a7f529653655632022-12-22T00:19:15ZengElsevierJournal of Advanced Research2090-12322019-11-01204350To reveal pharmacological targets and molecular mechanisms of curcumol against interstitial cystitisKa Wu0Pingyuan Wei1Meizhen Liu2Xiaoliu Liang3Min Su4Department of Pharmacy, The Second People's Hospital of Nanning City, The Third Affiliated Hospital of Guangxi Medical University, Nanning, PR ChinaDepartment of Pharmacy, Guigang City People's Hospital, The Eighth Affiliated Hospital of Guangxi Medical University, Guigang 537100, Guangxi, PR ChinaCollege of Pharmacy, Guangxi Medical University, Guangxi, Nanning 530021, PR ChinaCollege of Pharmacy, Guangxi Medical University, Guangxi, Nanning 530021, PR ChinaFaculty of Basic Medicine, Guilin Medical University, Huan Cheng North 2nd Road No. 109, Guilin 541004, PR China; Corresponding author.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-α), PTK2 and p-PTK2Tyr397 in human IC sections were observed, accompanied with altered urinary parameters. Interestingly, curcumol-treated IC mice showed that intracellular expressions of PTK2, p-PTK2Tyr397 in bladder samples were reduced, accompanied with lowered blood inflammatory cytokines of interleukin 6 (IL-6), TNF-α. 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. Keywords: Curcumol, Interstitial cystitis, Bioinformatics, Biomarkers, PTK2, protein-protein interactionhttp://www.sciencedirect.com/science/article/pii/S2090123219300918
spellingShingle Ka Wu
Pingyuan Wei
Meizhen Liu
Xiaoliu Liang
Min Su
To reveal pharmacological targets and molecular mechanisms of curcumol against interstitial cystitis
Journal of Advanced Research
title To reveal pharmacological targets and molecular mechanisms of curcumol against interstitial cystitis
title_full To reveal pharmacological targets and molecular mechanisms of curcumol against interstitial cystitis
title_fullStr To reveal pharmacological targets and molecular mechanisms of curcumol against interstitial cystitis
title_full_unstemmed To reveal pharmacological targets and molecular mechanisms of curcumol against interstitial cystitis
title_short To reveal pharmacological targets and molecular mechanisms of curcumol against interstitial cystitis
title_sort to reveal pharmacological targets and molecular mechanisms of curcumol against interstitial cystitis
url http://www.sciencedirect.com/science/article/pii/S2090123219300918
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