Therapeutic Effects of (5R)-5-Hydroxytriptolide on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via lncRNA WAKMAR2/miR-4478/E2F1/p53 Axis

Xinpeng Zhou, Duoli Xie, Jie Huang, Aiping LYU, Rongsheng Wang, Yehua Jin, Runrun Zhang, Cen Chang, Lingxia Xu, Linshuai Xu, Junyu Fan, Chao Liang, Dongyi He*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number605616
JournalFrontiers in Immunology
Volume12
DOIs
Publication statusPublished - 16 Feb 2021

Scopus Subject Areas

  • Immunology and Allergy
  • Immunology

User-Defined Keywords

  • (5R)-5-hydroxytriptolide
  • fibroblast-like synoviocytes
  • inflammation
  • miR-4478/E2F1/p53 axis
  • rheumatoid arthritis
  • WAKMAR2

Fingerprint

Dive into the research topics of 'Therapeutic Effects of (5R)-5-Hydroxytriptolide on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via lncRNA WAKMAR2/miR-4478/E2F1/p53 Axis'. Together they form a unique fingerprint.

Cite this