Identification of drug targets and potential molecular mechanisms for Wantong Jingu Tablet extract in treatment of rheumatoid arthritis: bioinformatics analysis of fibroblast-like synoviocytes
Abstract Background Rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLSs) play important roles in pathogenesis of rheumatoid arthritis (RA). Wantong Jingu Tablet (WJT), a mixture of traditional Chinese medicine, is a potentially effective therapy for RA, but its underlying mechanism is unclear...
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| Format: | Article |
| Language: | English |
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BMC
2020-06-01
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| Series: | Chinese Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s13020-020-00339-5 |
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| author | Zhaodong Li Fangyuan Qi Fan Li |
| author_facet | Zhaodong Li Fangyuan Qi Fan Li |
| author_sort | Zhaodong Li |
| collection | DOAJ |
| description | Abstract Background Rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLSs) play important roles in pathogenesis of rheumatoid arthritis (RA). Wantong Jingu Tablet (WJT), a mixture of traditional Chinese medicine, is a potentially effective therapy for RA, but its underlying mechanism is unclear. In this study, we explore the effects of WJT on human RA-FLSs and the underlying molecular mechanism. Methods The major components of WJT were determined using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Cell proliferative ability was evaluated by CCK-8, colony formation assay, and EdU incorporation assay. Cell apoptotic capacity was examined by caspase-3 and caspase-9 activity test. Protein levels of Bax and Bcl-2 were investigated by western blotting. High-throughput sequencing and bioinformatics analysis were conducted to screen and identify targeted genes, followed by identification by qRT-PCR and western blotting. Results In this study, we have identified 346 compounds in WJT. Our results showed that WJT inhibited the RA-FLSs proliferation, and promoted apoptosis in a dose- and time-dependent manner. More importantly, 184 differentially expressed genes (DEGs) has been screened after WJT treatment based on DEGSeq2 and 278 DEGs was identified by DEGSeq2 combined with WGCNA. Then, 10 hub genes were identified based on two different analyses, while the expression levels of only SMC3, THOC1, BUB1, and STAG2 were decreased after WJT treatment, which was identical to the sequencing profiles. Conclusions WJT exerted its anti-proliferation and pro-apoptosis effects possibly through suppressing the expression of SMC3, THOC1, BUB1, and STAG2 in RA-FLSs. Thus, therapeutics targeting these genes may be a promising strategy for rescuing RA. |
| first_indexed | 2024-12-22T22:47:59Z |
| format | Article |
| id | doaj.art-72c9a3da3bff4b9bad9d5955dbf07ee8 |
| institution | Directory Open Access Journal |
| issn | 1749-8546 |
| language | English |
| last_indexed | 2024-12-22T22:47:59Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Chinese Medicine |
| spelling | doaj.art-72c9a3da3bff4b9bad9d5955dbf07ee82022-12-21T18:10:01ZengBMCChinese Medicine1749-85462020-06-0115111310.1186/s13020-020-00339-5Identification of drug targets and potential molecular mechanisms for Wantong Jingu Tablet extract in treatment of rheumatoid arthritis: bioinformatics analysis of fibroblast-like synoviocytesZhaodong Li0Fangyuan Qi1Fan Li2Department of Pathogen Biology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medicine, Jilin UniversityDepartment of Pathogen Biology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medicine, Jilin UniversityDepartment of Pathogen Biology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medicine, Jilin UniversityAbstract Background Rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLSs) play important roles in pathogenesis of rheumatoid arthritis (RA). Wantong Jingu Tablet (WJT), a mixture of traditional Chinese medicine, is a potentially effective therapy for RA, but its underlying mechanism is unclear. In this study, we explore the effects of WJT on human RA-FLSs and the underlying molecular mechanism. Methods The major components of WJT were determined using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Cell proliferative ability was evaluated by CCK-8, colony formation assay, and EdU incorporation assay. Cell apoptotic capacity was examined by caspase-3 and caspase-9 activity test. Protein levels of Bax and Bcl-2 were investigated by western blotting. High-throughput sequencing and bioinformatics analysis were conducted to screen and identify targeted genes, followed by identification by qRT-PCR and western blotting. Results In this study, we have identified 346 compounds in WJT. Our results showed that WJT inhibited the RA-FLSs proliferation, and promoted apoptosis in a dose- and time-dependent manner. More importantly, 184 differentially expressed genes (DEGs) has been screened after WJT treatment based on DEGSeq2 and 278 DEGs was identified by DEGSeq2 combined with WGCNA. Then, 10 hub genes were identified based on two different analyses, while the expression levels of only SMC3, THOC1, BUB1, and STAG2 were decreased after WJT treatment, which was identical to the sequencing profiles. Conclusions WJT exerted its anti-proliferation and pro-apoptosis effects possibly through suppressing the expression of SMC3, THOC1, BUB1, and STAG2 in RA-FLSs. Thus, therapeutics targeting these genes may be a promising strategy for rescuing RA.http://link.springer.com/article/10.1186/s13020-020-00339-5Rheumatoid arthritisBioinformaticsFibroblast-like synoviocytesWantong Jingu Tablet |
| spellingShingle | Zhaodong Li Fangyuan Qi Fan Li Identification of drug targets and potential molecular mechanisms for Wantong Jingu Tablet extract in treatment of rheumatoid arthritis: bioinformatics analysis of fibroblast-like synoviocytes Chinese Medicine Rheumatoid arthritis Bioinformatics Fibroblast-like synoviocytes Wantong Jingu Tablet |
| title | Identification of drug targets and potential molecular mechanisms for Wantong Jingu Tablet extract in treatment of rheumatoid arthritis: bioinformatics analysis of fibroblast-like synoviocytes |
| title_full | Identification of drug targets and potential molecular mechanisms for Wantong Jingu Tablet extract in treatment of rheumatoid arthritis: bioinformatics analysis of fibroblast-like synoviocytes |
| title_fullStr | Identification of drug targets and potential molecular mechanisms for Wantong Jingu Tablet extract in treatment of rheumatoid arthritis: bioinformatics analysis of fibroblast-like synoviocytes |
| title_full_unstemmed | Identification of drug targets and potential molecular mechanisms for Wantong Jingu Tablet extract in treatment of rheumatoid arthritis: bioinformatics analysis of fibroblast-like synoviocytes |
| title_short | Identification of drug targets and potential molecular mechanisms for Wantong Jingu Tablet extract in treatment of rheumatoid arthritis: bioinformatics analysis of fibroblast-like synoviocytes |
| title_sort | identification of drug targets and potential molecular mechanisms for wantong jingu tablet extract in treatment of rheumatoid arthritis bioinformatics analysis of fibroblast like synoviocytes |
| topic | Rheumatoid arthritis Bioinformatics Fibroblast-like synoviocytes Wantong Jingu Tablet |
| url | http://link.springer.com/article/10.1186/s13020-020-00339-5 |
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