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WGCNA and molecular docking reveal key hub genes and potential natural inhibitor in interstitial cystitis/bladder pain syndrome

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Abstract

Introduction and hypothesis

The etiology and treatment of interstitial cystitis/bladder pain syndrome are still controversial. The purpose of this study is to determine the key genes and specific regulatory pathways related to it and to find potential drug-active components through integrated bioinformatics.

Methods

The data set GSE11783 was downloaded from GEO database. The modules significantly related to interstitial cystitis/bladder pain syndrome were identified by weighted correlation network analysis. The genes in the key modules were analyzed by functional enrichment and protein interaction by Cytoscape software, and finally the core hub genes were screened. Furthermore, the molecular docking verification of active components and key proteins was carried out by using AutoDock Vin software.

Results

Among the 14 modules derived from WGCNA, turquoise module had the highest correlation with IC/BPS (r = 0.85, P < 0.001). The genes in the module were mainly enriched in the biological processes such as the interaction between cytokines and cytokine receptors and chemokine signaling pathway. The genes in the related modules of differentially expressed genes and WGCNA traits were intersected to obtain the core hub genes. Protein-protein interaction network analysis showed that the key genes were upregulated genes CCR7 and CCL19. In terms of molecular docking, triptolide, the active component in the traditional anti-inflammatory drug Tripterygium wilfordii, can form effective molecular binding with both core hub genes.

Conclusions

Our study identified the core hub genes CCR7 and CCL19, which acted as essential components in interstitial cystitis/bladder pain syndrome. Furthermore, CCR7 and CCL19 can form effective binding with triptolide, which will provide new insights into the development of new therapies for interstitial cystitis/bladder pain syndrome.

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Abbreviations

IC/BPS:

Interstitial cystitis/bladder pain syndrome

WGCNA:

Weighted gene co-expression network analysis

DEG:

differentially expressed gene

GO:

Gene ontology

KEGG:

Kyoto Encyclopedia of Genes and Genomes

PPI:

Protein-protein interaction

ME:

Module eigengene

MS:

Module signifcance

GS:

Gene signifcance

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Funding

This work was funded by the National Natural Science Foundation of China (grant numbers 81702528 and 82072841).

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Authors and Affiliations

  1. Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yan Jiang West Road, Guangzhou, 510120, China

    Kuiqing Li, Cong Lai, Cheng Liu, Zhuohang Li, Kaixuan Guo & Kewei Xu

Authors
  1. Kuiqing Li
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  2. Cong Lai
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  3. Cheng Liu
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  4. Zhuohang Li
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  5. Kaixuan Guo
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  6. Kewei Xu
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Contributions

KQ Li: Protocol development, Data analysis, Manuscript writing,

C Lai: Protocol development, Data analysis, Manuscript writing.

C Liu: Data collection and management.

ZH Li: Data collection and management.

KX Guo: Data analysis.

KW Xu: Protocol development.

Corresponding author

Correspondence to Kewei Xu.

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Supplementary Information

Additional file 1

One hundred fifty-eight overlapped hub genes. List of intersection genes between differentially expressed genes of GSE11783 and turquoise module. (XLSX 10 kb)

Additional file 2

CIBERSORT results. Proportion of 22 kinds of immune cells in IC/BPS and control samples. (XLSX 11 kb)

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Li, K., Lai, C., Liu, C. et al. WGCNA and molecular docking reveal key hub genes and potential natural inhibitor in interstitial cystitis/bladder pain syndrome. Int Urogynecol J 33, 2241–2249 (2022). https://doi.org/10.1007/s00192-022-05113-9

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  • DOI: https://doi.org/10.1007/s00192-022-05113-9

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