2. Academic Validation
  3. Up-regulated DERL3 in fibroblast-like synoviocytes exacerbates inflammation of rheumatoid arthritis

Up-regulated DERL3 in fibroblast-like synoviocytes exacerbates inflammation of rheumatoid arthritis

  • Clin Immunol. 2020 Nov;220:108579. doi: 10.1016/j.clim.2020.108579.
Manman Geng 1,  Ke Xu 2,  Liesu Meng 1,  Jing Xu 3,  Congshan Jiang 3,  Yuanxu Guo 3,  Xiaoyu Ren 2,  Xiaowei Li 3,  Yizhao Peng 3,  Si Wang 3,  Fumeng Huang 3,  Jing Zhang 3,  Xipeng Wang 3,  Wenhua Zhu 4,  Shemin Lu 5
Affiliations

Affiliations

  • 1 Institute of Molecular and Translational Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Xi'an, China.
  • 2 Xi'an Hong Hui Hospital, the Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, China.
  • 3 Institute of Molecular and Translational Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.
  • 4 Institute of Molecular and Translational Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Xi'an, China. Electronic address: [email protected].
  • 5 Institute of Molecular and Translational Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Xi'an, China. Electronic address: [email protected].
PMID: 32866644 DOI: 10.1016/j.clim.2020.108579
Abstract

Endoplasmic reticulum (ER) stress associated proteins contribute to the pathogenesis of rheumatoid arthritis (RA) through affecting synoviocyte proliferation and proinflammatory cytokine production. The role of DERL3, an ER-associated degradation component, in joint inflammation of RA was explored. Synovial tissues from RA and osteoarthritis (OA) patients were collected, and in RA synovial tissue, DERL3 showed up-regulation and significantly positive correlation with the expression of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and matrix metalloproteinase (MMP)-1. Immunofluorescence result suggested DERL3 was located in fibroblast-like synoviocytes (FLS). Among different inflammatory stimuli, DERL3 could be up-regulated by TNF-α stimulation in FLS. Under TNF-α stimulation, knocking down DERL3, the expression of IL-6, IL-8, MMP-1, MMP-13 was reduced and the activation of nuclear factor kappa B (NF-κB) signaling pathway was inhibited. In pristane-induced arthritis (PIA) rat model, Derl3 was up-regulated in synovial tissue and disease was attenuated after intraarticular injection of siDerl3. Overall, we conclude that TNF-α inducing DERL3 expression promotes the inflammation of FLS through activation of NF-κB signaling pathway, suggesting DERL3 plays important roles in the pathogenesis of RA and is a promising therapeutic target.

Keywords

DERL3; Fibroblast-like synoviocytes; PIA; Rheumatoid arthritis; TNF-α.

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