Affordable Access

deepdyve-link
Publisher Website

Sonic Hedgehog Regulates Proliferation, Migration and Invasion of Synoviocytes in Rheumatoid Arthritis via JNK Signaling

Authors
  • Zhu, Shangling1
  • Ye, Yuanmei1
  • Shi, Yiming2
  • Dang, Junlong3
  • Feng, Xiaoxue1
  • Chen, Yingdi1
  • Liu, Fang1
  • Olsen, Nancy4
  • Huang, Jianlin1
  • Zheng, Song Guo5
  • 1 Department of Rheumatology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou , (China)
  • 2 Department of Internal Care Unit, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou , (China)
  • 3 Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou , (China)
  • 4 Department of Medicine, Penn State Hershey Medical Center, Hershey, PA , (United States)
  • 5 Department of Internal Medicine, Ohio State University College of Medicine and Wexner Medical Center, Columbus, OH , (United States)
Type
Published Article
Journal
Frontiers in Immunology
Publisher
Frontiers Media SA
Publication Date
Jun 24, 2020
Volume
11
Identifiers
DOI: 10.3389/fimmu.2020.01300
PMID: 32670287
PMCID: PMC7326768
Source
PubMed Central
Keywords
License
Unknown

Abstract

Activated fibroblast-like synoviocytes (FLSs) play a central role in the formation of synovial pannus and joint destruction in rheumatoid arthritis (RA). Targeting FLSs could be a potential therapeutic strategy. The objective of this study is to explore the role of c-Jun N-terminal kinase (JNK) in proliferation, migration and invasion of FLSs promoted by the sonic hedeghog (SHH) signaling pathway in patients with RA. Activation of SHH signaling was evaluated by real-time PCR and Western Blot. Levels of phosphorylation of JNK and c-Jun were detected by Western Blot. FLSs proliferation was quantified by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Cell migration and invasion were assessed by wound healing assay and Transwell chamber assay. Invasiveness of FLSs in vivo was evaluated using a humanized synovitis animal model. We observed that treatment of SHH agonist (SAG) significantly increased the levels of phosphorylation of JNK and c-Jun, while SHH antagonist (cyclopamine) significantly decreased the expression of phospho-JNK and phospho-c-Jun in FLSs. The elevated level of phospho-c-Jun stimulated by SAG was decreased in the presence of JNK inhibitor (SP600125) ( P < 0.001). FLSs proliferation, migration and invasion were promoted by SHH agonist ( P < 0.05). However, the enhanced aggressiveness of FLSs was abolished in the presence of JNK inhibitor ( P < 0.05). In vivo study showed that the invasion of FLSs into cartilage was increased by SHH overexpression and the excessive invasiveness was inhibited by blockade of JNK signaling ( P < 0.01). These results suggest that JNK is one of the downstream molecules mediating the effect of SHH signaling in FLSs. These findings indicate that SHH-JNK signaling could be a potential therapeutic target to suppress the aggressiveness of FLSs and prevent articular damage of RA.

Report this publication

Statistics

Seen <100 times