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Integrating Transcriptomics, Proteomics, and Metabolomics Profiling with System Pharmacology for the Delineation of Long-Term Therapeutic Mechanisms of Bufei Jianpi Formula in Treating COPD

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ABSTRACT

In previous work, we identified 145 active compounds from Bufei Jianpi formula (BJF) by system pharmacology and found that BJF showed short-term effect on chronic obstructive pulmonary disease (COPD) rats. Here, we applied the transcriptomic, proteomic, and metabolomics approaches to illustrate the long-term anti-COPD action and its system mechanism of BJF. BJF has obvious anti-COPD effect through decreasing inflammatory cytokines level, preventing protease-antiprotease imbalance and collagen deposition on week 32 by continuous oral administration to rats from weeks 9 to 20. Subsequently, applying the transcriptomic, proteomic, and metabolomics techniques, we detected a number of regulated genes, proteins, and metabolites, mainly related to antioxidant activity, focal adhesion, or lipid metabolism, in lung tissues of COPD and BJF-treated rats. Afterwards, we integrated system pharmacology target, transcript, protein, and metabolite data sets and found that many genes, proteins, and metabolites in rats BJF-treated group and the target proteins of BJF were mainly attributed to lipid metabolism, inflammatory response, oxidative stress, and focal adhesion. Taken together, BJF displays long-term anti-COPD effect probably by system regulation of the lipid metabolism, inflammatory response pathways oxidative stress, and focal adhesion.

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ClueGO analysis of molecular functions of regulated genes in COPD rat and BJF-treated rat lung tissues. (a) The molecular functions of regulated genes in COPD rats. (b) The molecular functions of regulated genes in BJF-treated rats. Functionally grouped network of enriched categories was generated for the regulated genes.
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fig7: ClueGO analysis of molecular functions of regulated genes in COPD rat and BJF-treated rat lung tissues. (a) The molecular functions of regulated genes in COPD rats. (b) The molecular functions of regulated genes in BJF-treated rats. Functionally grouped network of enriched categories was generated for the regulated genes.

Mentions: The microarray-based RNA expression analysis was performed. Of the 41000 genes profiled, 976 and 2857 exhibited significant alterations in COPD model rats (versus control) and BJF treatment rats (versus COPD model), respectively (see Supplementary Tables  A1 and A2 available online at https://doi.org/10.1155/2017/7091087). We found these genes were related to many biological functions, such as oxidoreductase, ion channel, or metalloendopeptidase activity (Figure 7). Then, we performed the gene set enrichment analysis and found many significantly altered pathways at mRNA expression level (Tables 1 and 2).


Integrating Transcriptomics, Proteomics, and Metabolomics Profiling with System Pharmacology for the Delineation of Long-Term Therapeutic Mechanisms of Bufei Jianpi Formula in Treating COPD
ClueGO analysis of molecular functions of regulated genes in COPD rat and BJF-treated rat lung tissues. (a) The molecular functions of regulated genes in COPD rats. (b) The molecular functions of regulated genes in BJF-treated rats. Functionally grouped network of enriched categories was generated for the regulated genes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382313&req=5

fig7: ClueGO analysis of molecular functions of regulated genes in COPD rat and BJF-treated rat lung tissues. (a) The molecular functions of regulated genes in COPD rats. (b) The molecular functions of regulated genes in BJF-treated rats. Functionally grouped network of enriched categories was generated for the regulated genes.
Mentions: The microarray-based RNA expression analysis was performed. Of the 41000 genes profiled, 976 and 2857 exhibited significant alterations in COPD model rats (versus control) and BJF treatment rats (versus COPD model), respectively (see Supplementary Tables  A1 and A2 available online at https://doi.org/10.1155/2017/7091087). We found these genes were related to many biological functions, such as oxidoreductase, ion channel, or metalloendopeptidase activity (Figure 7). Then, we performed the gene set enrichment analysis and found many significantly altered pathways at mRNA expression level (Tables 1 and 2).

View Article: PubMed Central - PubMed

ABSTRACT

In previous work, we identified 145 active compounds from Bufei Jianpi formula (BJF) by system pharmacology and found that BJF showed short-term effect on chronic obstructive pulmonary disease (COPD) rats. Here, we applied the transcriptomic, proteomic, and metabolomics approaches to illustrate the long-term anti-COPD action and its system mechanism of BJF. BJF has obvious anti-COPD effect through decreasing inflammatory cytokines level, preventing protease-antiprotease imbalance and collagen deposition on week 32 by continuous oral administration to rats from weeks 9 to 20. Subsequently, applying the transcriptomic, proteomic, and metabolomics techniques, we detected a number of regulated genes, proteins, and metabolites, mainly related to antioxidant activity, focal adhesion, or lipid metabolism, in lung tissues of COPD and BJF-treated rats. Afterwards, we integrated system pharmacology target, transcript, protein, and metabolite data sets and found that many genes, proteins, and metabolites in rats BJF-treated group and the target proteins of BJF were mainly attributed to lipid metabolism, inflammatory response, oxidative stress, and focal adhesion. Taken together, BJF displays long-term anti-COPD effect probably by system regulation of the lipid metabolism, inflammatory response pathways oxidative stress, and focal adhesion.

No MeSH data available.


Related in: MedlinePlus