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: 114

Antifibrotic Regulation By Response Gene to Complement 32 Protein

Sergei Atamas, Violeta Rus, Virginia Lockatell, Horea Rus and Irina Luzina, University of Maryland School of Medicine, Baltimore, MD

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Fibroblasts, fibrosis, Lung, mechanisms and scleroderma

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

Date: Sunday, October 21, 2018

Title: Systemic Sclerosis and Related Disorders – Basic Science Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Pulmonary fibrosis is a serious problem in patients with scleroderma lung disease (SLD). Better therapies for pulmonary fibrosis are urgently needed. Identification of new therapeutic targets guides the development of innovative therapies for patients with pulmonary fibrosis. Previous research suggested that a protein termed Response Gene to Complement 32 (RGC-32) is involved in kidney fibrosis, but RGC-32 involvement in SLD or other forms of pulmonary fibrosis has not been explored in depth.

Methods: The levels of RGC-32 mRNA and protein in human lung tissues were studied by RNA-Seq, qRT-PCR, and Western blotting. A chronic bleomycin exposure model of pulmonary fibrosis was used to assess the effects of RGC-32 gene deficiency on collagen accumulation in the lungs in vivo. Experiments in primary human lung fibroblast cultures were used to investigate the effect of plasmid-based RGC-32 gene delivery on TGF-β-induced upregulation of collagen mRNA and protein.

Results: The RNA-Seq data suggested and qRT-PCR confirmed a significant decline in the levels of RGC-32 mRNA in the lung tissues of patients with SLD and idiopathic pulmonary fibrosis (IPF) compared with lung tissues from healthy controls. Similarly, RGC-32 protein levels were significantly decreased in SLD and IPF lung tissues based on western blotting analyses. These observations contrasted previous reports about RGC-32 involvement in several non-fibrotic diseases as well as in kidney fibrosis, all of which implicated elevated levels of RGC-32 in disease mechanisms. In an attempt to explain the striking difference between the commonly observed elevation of RGC-32 level in a variety of diseases and the observed decline in pulmonary RGC-32 mRNA and protein in patients with SLD and IPF, the possibility was considered that the decrease in RGC-32 in pulmonary fibrosis might be part of a failing protective feedback loop in which lower RGC-32 levels represent the organism’s attempt to attenuate profibrotic signaling. To assess this possibility, germline-deficient (RGC-32–/–) mice were challenged with bleomycin. The expectation was that if RGC-32 is a profibrotic mediator as suggested by the studies of kidney fibrosis, then RGC-32–/– mice would be protected from bleomycin-induced fibrosis compared with their wild-type RGC-32+/+ strain background controls. However, RGC-32–/– mice were not only not protected from fibrosis, but accumulated significantly more collagen in response to bleomycin challenge, indicating that RGC-32 acts protectively against fibrosis in the lungs. Further supporting this notion, overexpression of RGC-32 attenuated TGF-β-induced upregulation of collagen in primary human lung fibroblast cultures.

Conclusion: These combined data from human patients, the animal model, and cultured primary fibroblasts indicate that RGC-32 protects from fibrosis in the lung and that its loss in patients with SLD and IPF allows for a more severe fibrosis. Therapeutic restoration of pulmonary RGC-32 levels may be beneficial for patients with pulmonary fibrosis.


Disclosure: S. Atamas, None; V. Rus, None; V. Lockatell, None; H. Rus, None; I. Luzina, None.

To cite this abstract in AMA style:

Atamas S, Rus V, Lockatell V, Rus H, Luzina I. Antifibrotic Regulation By Response Gene to Complement 32 Protein [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/antifibrotic-regulation-by-response-gene-to-complement-32-protein/. Accessed .
  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/antifibrotic-regulation-by-response-gene-to-complement-32-protein/

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