Daniel Vukaj
Research Mentor: Eliza Tsou
Mentor Department: Internal Medicine, Medicine
Author(s): Daniel Vukaj, Alexander Cai, Sunny Kataria, Neha Khanna, Michael Konadu, Alyssa Rosek, Amanda Slagle, Caroline Foster, Eliza Tsou
Session: Session 6 (3:00 PM – 3:50 PM)
Presentation Type: Poster 121
Abstract
Systemic sclerosis (SSc), also known as scleroderma, is a severe autoimmune disease characterized by excessive collagen production and progressive fibrosis of the skin and internal organs. Recent research suggests that RNA methylation, an epigenetic mechanism that regulates RNA stability and gene expression, may play a role in fibrotic diseases. However, the role of RNA methylation in systemic sclerosis has not been studiedextensively yet. This project investigates whether inhibiting the RNA demethylase FTO can reduce fibrotic activity in in vitro and in vivo models of SSc. To examine this, dermal fibroblasts isolated from SSc patient skin biopsies were treated with the FTO inhibitor FB23. Gene expression changes were analyzed using bulk RNA sequencing. Additionally, a bleomycin-induced skin fibrosis mouse model was used to mimic skin fibrosis. Mice were treated with bleomycin intradermally to induce fibrosis and administration of FB23 intraperitoneally at the same time to evaluate whether inhibition of FTO prevents dermal thickening. Analysis of RNA-seq results indicate that treatment with FB23 reduced the expression of fibrotic genes, including extracellular matrix genes and ACTA2, a marker associated with collagen production and myofibroblast activity. In the mouse model, FB23 treatment prevented the increase in dermal thickness caused by bleomycin. These findings suggest that RNA methylation plays an important role in fibrosis and that targeting the FTO enzyme may be a new therapeutic strategy for treating SSc.
