Frontiers in Immunology (Feb 2021)
Therapeutic Effects of (5R)-5-Hydroxytriptolide on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via lncRNA WAKMAR2/miR-4478/E2F1/p53 Axis
- Xinpeng Zhou,
- Xinpeng Zhou,
- Xinpeng Zhou,
- Duoli Xie,
- Jie Huang,
- Aiping Lu,
- Aiping Lu,
- Aiping Lu,
- Rongsheng Wang,
- Rongsheng Wang,
- Yehua Jin,
- Yehua Jin,
- Runrun Zhang,
- Runrun Zhang,
- Cen Chang,
- Cen Chang,
- Lingxia Xu,
- Lingxia Xu,
- Linshuai Xu,
- Linshuai Xu,
- Junyu Fan,
- Chao Liang,
- Dongyi He,
- Dongyi He
Affiliations
- Xinpeng Zhou
- Department of Rheumatology, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Xinpeng Zhou
- Department of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai, China
- Xinpeng Zhou
- Department of Rheumatology, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine (TCM), Jinan, China
- Duoli Xie
- School of Chinese Medicine, Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, Hong Kong Baptist University, Hong Kong, China
- Jie Huang
- Department of Biology, Southern University of Science and Technology, Shenzhen, China
- Aiping Lu
- School of Chinese Medicine, Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, Hong Kong Baptist University, Hong Kong, China
- Aiping Lu
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
- Aiping Lu
- Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, China
- Rongsheng Wang
- Department of Rheumatology, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Rongsheng Wang
- Department of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai, China
- Yehua Jin
- Department of Rheumatology, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Yehua Jin
- Department of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai, China
- Runrun Zhang
- Department of Rheumatology, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Runrun Zhang
- Department of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai, China
- Cen Chang
- Department of Rheumatology, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Cen Chang
- Department of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai, China
- Lingxia Xu
- Department of Rheumatology, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Lingxia Xu
- Department of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai, China
- Linshuai Xu
- Department of Rheumatology, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Linshuai Xu
- Department of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai, China
- Junyu Fan
- Department of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai, China
- Chao Liang
- Department of Biology, Southern University of Science and Technology, Shenzhen, China
- Dongyi He
- Department of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai, China
- Dongyi He
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
- DOI
- https://doi.org/10.3389/fimmu.2021.605616
- Journal volume & issue
-
Vol. 12
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease. Fibroblast-like synoviocytes (FLS) serve a major role in synovial hyperplasia and inflammation in RA. (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide derivative, shows promising therapeutic effects for RA and is now in phase II clinical trials in China. However, the underlying mechanism of LLDT-8 is still not fully understood. Here, we found that LLDT-8 inhibited proliferation and invasion of RA FLS, as well as the production of cytokines. Microarray data demonstrated that LLDT-8 upregulated the expression of long non-coding RNA (lncRNA) WAKMAR2, which was negatively associated with proliferation and invasion of RA FLS, as well as the production of pro-inflammatory cytokines. Knockdown of WAKMAR2 abolished the inhibitory effects of LLDT-8 on RA FLS. Mechanistically, WAKMAR2 sponged miR-4478, which targeted E2F1 and downstreamed p53 signaling. Rescue experiments indicated that the inhibitory effects of LLDT-8 on RA FLS were dependent on WAKMAR2/miR-4478/E2F1/p53 axis.
Keywords
- rheumatoid arthritis
- (5R)-5-hydroxytriptolide
- fibroblast-like synoviocytes
- inflammation
- WAKMAR2
- miR-4478/E2F1/p53 axis
