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: 1044

TGF-β Isoforms Modulate the RNA Cargo of Extracellular Vesicles (Exosomes) Isolated from Cultured Normal Human Lung Microvascular Endothelial Cells: A Mechanistic Link Between Endothelial Cell Dysfunction and the Establishment of a Profibrotic Phenotype in SSc?

Peter Wermuth1 and Sergio Jimenez 1, 1Jefferson Institute of Molecular Medicine and Division of Connective Tissue Diseases, Thomas Jefferson University, Philadelphia, PA, Philadelphia, PA

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: endothelial cells, fibrosis, Systemic sclerosis, transforming growth factor and exosome

  • Tweet
  • Email
  • Print
Session Information

Date: Monday, November 11, 2019

Title: Systemic Sclerosis & Related Disorders – Basic Science Poster

Session Type: Poster Session (Monday)

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

Background/Purpose: Extracellular vesicles (EV) are a diverse assortment of lipid bilayer-bound vesicles of various sizes and origin. Exosomes are a subset of EV arising from multivesicular bodies released into the extracellular space and into the circulation that contain various macromolecules including numerous microRNA (miRNA) and proteins. EV can mediate intercellular communication by fusing and releasing their macromolecular contents into target cells. The mechanism of the establishment and progression of a profibrotic phenotype in Systemic Sclerosis (SSc) is not currently well understood. Microvascular damage is considered an early event in SSc pathogenesis and EV produced by damaged microvascular endothelial cells may represent an important component in the initiation and progression of SSc.  Here, we characterized the miRNA content of EV isolated from cultured normal human lung microvascular endothelial cells (HLMVEC) treated with TGF-β1, TGF-β2, or TGF-β3 to determine the specific influence of the TGF-β isoforms on the RNA content of HLMVEC.

Methods: Commercially obtained normal HLMVEC were treated with 10 ng/ml of TGF-β1, TGF-β2, or TGF-β3 in FBS-free media. Culture media was isolated from duplicate wells after 72h and EV were isolated by resin-based purification. Total EV RNA was isolated and RNA sequencing (RNA-seq) was performed by 50bp paired-end RNA-seq at 10-20 million reads per sample and aligned to the reference genome (hg19). Differential analysis of RNA content was performed by comparing each treatment group to untreated cells using OASIS 2.0. Gene set enrichment and pathway analysis of miRNA targets was performed employing the MirPath v3.0. Differential expression of selected EV RNA was verified by qPCR.

Results: Treatment of cultured normal HLMVEC with TGF-β isoforms altered the RNA contents of EV isolated from these cells. In addition to changes in miRNA content, marked differences in the amounts and identity of other classes of small RNA such as piRNA were induced upon treatment with the TGF-β isoforms. Analysis of EV miRNA targets indicated extracellular matrix (ECM)-receptor interactions, proteoglycans, ECM components and TGF-β signaling were among the most significantly targeted pathways.

Conclusion: Despite similarities in structure and sequence, TGF-β protein isoforms result in distinct populations of HLMVEC-derived EV. The pattern of upregulated and downregulated EV miRNA from TGF-β1- and TGF-β3-treated HLMVEC show considerable overlap compared with TGF-β2-treated HLMVEC. However, each TGF-β isoform mediated distinct patterns and levels of EV small RNA species. Pathway analysis revealed that numerous pathways are regulated by all three isoforms although the individual genes affected and the magnitude of the changes produced differed for each specific TGF-β isoform. The pathways targeted indicate that EV miRNA could affect target cells by altering the pathways involved in extracellular matrix synthesis, potentially inducing a profibrotic phenotype in target cells. This mechanism may explain the extension of SSc-associated pathological alterations from afftected to normal tissues.


Disclosure: P. Wermuth, None; S. Jimenez, None.

To cite this abstract in AMA style:

Wermuth P, Jimenez S. TGF-β Isoforms Modulate the RNA Cargo of Extracellular Vesicles (Exosomes) Isolated from Cultured Normal Human Lung Microvascular Endothelial Cells: A Mechanistic Link Between Endothelial Cell Dysfunction and the Establishment of a Profibrotic Phenotype in SSc? [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/tgf-%ce%b2-isoforms-modulate-the-rna-cargo-of-extracellular-vesicles-exosomes-isolated-from-cultured-normal-human-lung-microvascular-endothelial-cells-a-mechanistic-link-between-endothelial-cell-dy/. Accessed .
  • Tweet
  • Email
  • Print

« Back to 2019 ACR/ARP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/tgf-%ce%b2-isoforms-modulate-the-rna-cargo-of-extracellular-vesicles-exosomes-isolated-from-cultured-normal-human-lung-microvascular-endothelial-cells-a-mechanistic-link-between-endothelial-cell-dy/

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