Abstract |
Tripterygium is a traditional Chinese medicine that has widely been used in the treatment of rheumatic disease. (5R)-5-hydroxytriptolide (LLDT-8) is an extracted compound from Tripterygium, which has been shown to have lower cytotoxicity and relatively higher immunosuppressive activity when compared to Tripterygium. However, our understanding of LLDT-8-induced epigenomic impact and overall regulatory changes in key cell types remains limited. Doing so will provide critically important mechanistic information about how LLDT-8 wields its immunosuppressive activity. The purpose of this study was to assess the effects of LLDT-8 on transcriptome including mRNAs and long non-coding RNA (lncRNAs) in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) by a custom genome-wide microarray assay. Significant differential expressed genes were validated by QPCR. Our work shows that 394 genes (281 down- and 113 up-regulated) were significantly differentially expressed in FLS responding to the treatment of LLDT-8. KEGG pathway analysis showed 20 pathways were significantly enriched and the most significantly enriched pathways were relevant to Immune reaction, including cytokine- cytokine receptor interaction (P = 4.61 × 10-13), chemokine signaling pathway (P = 1.01 × 10-5) and TNF signaling pathway (P = 2.79 × 10-4). Furthermore, we identified 618 highly negatively correlated lncRNA- mRNA pairs from the selected significantly differential lncRNA and mRNA including 27 cis-regulated and 591 trans-regulated lncRNA-mRNAs modules. KEGG and GO based function analysis to differential lncRNA also shown the enrichment of immune response. Finally, lncRNA- transcription factor (TF) and lncRNA-TF- mRNA co-expression network were constructed with high specific network characteristics, indicating LLDT-8 would influence the expression network within the whole FLS cells. The results indicated that the LLDT-8 would mainly influence the FLS cells systemically and specially in the process of immune related pathways.
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Authors | Shicheng Guo, Jia Liu, Ting Jiang, Dungyang Lee, Rongsheng Wang, Xinpeng Zhou, Yehua Jin, Yi Shen, Yan Wang, Fengmin Bai, Qin Ding, Grace Wang, Jianyong Zhang, Xiaodong Zhou, Steven J Schrodi, Dongyi He |
Journal | Scientific reports
(Sci Rep)
Vol. 9
Issue 1
Pg. 11155
(08 01 2019)
ISSN: 2045-2322 [Electronic] England |
PMID | 31371761
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 5-hydroxytriptolide
- Cytokines
- Diterpenes
- Immunosuppressive Agents
- RNA, Long Noncoding
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Topics |
- Arthritis, Rheumatoid
(drug therapy, pathology)
- Cytokines
(metabolism)
- Diterpenes
(pharmacology)
- Epigenomics
- Female
- Fibroblasts
- Gene Expression Regulation
(drug effects)
- Humans
- Immunity
(drug effects, genetics)
- Immunosuppressive Agents
(pharmacology)
- Male
- RNA, Long Noncoding
- Synoviocytes
(immunology)
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