ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 92

Long Noncoding RNA Nron Regulates the Activity of NFAT5 through Ubiquitin-Independent Proteasome Pathway in Rheumatoid Arthritis

Kunihiko Umekita1,2, Michelle Trenkmann1, Christoph Kolling3, Akihiko Okayama4, Renate Gay1, Steffen Gay1 and Mojca Frank Bertoncelj5, 1Center of Experimental Rheumatology, University Hospital Zurich and Zurich Center of Integrative Human Physiology (ZIHP), Zurich, Switzerland, 2Department of Rheumatology, Infectious diseases and Laboratory medicine, University of Miyazaki, Miyazaki, Japan, 3Schulthess Clinic, Zurich, Switzerland, 4Department of Rheumatology, Infectious Diseases and Laboratory Medicine, University of Miyazaki, Miyazaki, Japan, 5Center of Experimental Rheumatology, University Hospital Zurich, Zurich, Switzerland

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Epigenetics, proteomics, rheumatoid arthritis (RA) and transcription factor

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Title: Genetics, Genomics and Proteomics I

Session Type: Abstract Submissions (ACR)

Background/Purpose: Long noncoding RNAs (lncRNAs) are increasingly recognized as master regulators of gene expression. The lncRNA NRON, noncoding repressor of nuclear factor of activated T cells (NFAT) can repress the cytoplasmic-nuclear translocation and function of NFAT1-4 transcriptional factors. Recently, we have reported that NRON regulates also the activity of NFAT5, affecting thereby the function of rheumatoid arthritis synovial fibroblasts (RASF). In addition, the ubiquitin-independent proteasome system has been shown to play an important role in regulating the cellular levels of NFAT5. Our objective was to investigate the regulation of NRON levels in RASF and to explore the role of NRON in protein turnover of NFAT5.

Methods: The levels and subcellular localization of NFAT5 protein in RASF were analyzed by Western blotting using α-tubulin for normalization. RASF were transfected with siRNA targeting NRON or scrambled siRNA using Lipofectamine 2000. RASF were treated with TNFα (10ng/ml), p38MAPK inhibitor (p38i, 10uM) SB202190, and/or proteasome inhibitor MG132 (1.0uM). Gene expression was measured by quantitative real-time PCR with normalization to GAPDH or β2-microglobulin. ELISA was used to measure IL-6 secretion from RASF.

Results: The levels of NRON were significantly decreased and the levels of NFAT5 protein were increased in RASF after 2hr of TNFα stimulation, while the levels of NFAT5 mRNA were not changed. Down regulation of NRON after silencing or TNFα stimulation was accompanied by the translocation of NFAT5 from the cytoplasm to the nucleus of RASF, increasing the transcription of known NFAT5 target genes, such as IL-6 (x-fold±SD: 3.0±2.2, p=0.03, n=4;) and MMP13 (x-fold±SD: 4.7±2.0, p=0.03, n=4). The secretion of IL-6 in the culture medium of RASF was also significantly increased (mean±S.D: 1676±479 vs 2433±504 pg/mL, p=0.007, n=5). The treatment of RASF with p38i significantly repressed not only the TNFα-induced up regulation of IL-6 but also the TNFα-induced down regulation of NRON (p= 0.001 and p= 0.04, n=5, respectively). Additionally, the proteasome-dependent degradation of NFAT5 was significantly enhanced by p38i (p= 0.01, n=5). Blocking the proteasome activity by MG132 inhibited the p38-induced degradation of NFAT5. Furthermore, the p38i-induced degradation of NFAT5 was inhibited also after silencing of NRON in RASF.

Conclusion: Our data show that TNFα down regulates the expression of lncRNA NRON in RASF by enhancing the activity of p38MAPK. Down regulation of NRON not only enhances the nuclear translocation and transcriptional activity of NFAT5 but also increases the total amount of NFAT5 in RASF by influencing the turnover of NFAT5 via ubiquitin-independent proteasome system. This novel data show the complex and multilevel capacities of the lncRNA NRON in regulating the function of NFAT5, thereby promoting proinflammatory and matrix-destructive responses of RASF.


Disclosure:

K. Umekita,

IMI BTCure, EuroTEAM, IAR,

2;

M. Trenkmann,
None;

C. Kolling,
None;

A. Okayama,
None;

R. Gay,
None;

S. Gay,
None;

M. Frank Bertoncelj,

IMI BTCure, EuroTEAM, IAR,

2.

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/long-noncoding-rna-nron-regulates-the-activity-of-nfat5-through-ubiquitin-independent-proteasome-pathway-in-rheumatoid-arthritis/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology