Alisa Zhavoronkova
Pronouns:
Research Mentor(s): Thomas Sisson
Co-Presenter:
Research Mentor School/College/Department: Internal Medicine / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 6 – 4:40pm – 5:30 pm
Room: League Ballroom
Authors: Alisa Zhavoronkova, Thomas Sisson, Natalya Subbotina
Presenter: 53
Abstract
Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with a median survival of 3.5 years, affecting ~89,000 people in the United States. IPF leads to excessive deposition of collagen proteins and progressive scarring, making the lungs unable to transport oxygen into the bloodstream effectively. Current treatments are aimed at preventing scarring and relieving symptoms. IPF is characterized by growth factor-dependent differentiation of lung fibroblasts into myofibroblasts, which are associated with the synthesis and secretion of ECM molecules including collagen. This differentiation of fibroblasts into myofibroblasts leading to ECM accumulation in tissues is promoted by TGF-ß (transforming growth factor-ß) and other profibrotic growth factors. It has previously been shown that TGF-ß (transforming growth factor-ß) induces plasminogen activator inhibitor-1 (PAI-1) production; however, it is unknown whether PAI-1 and Sortilin related receptor (SorlA), a PAI-1 binding target in the fibrotic lung, are required for myofibroblast differentiation. We investigated how different concentrations of TGF-ß and CTGF (connective tissue growth factor) affect cell proliferation and the expression of PAI-1 and SorlA. Normal human lung fibroblasts (NHLF) were cultured and treated with different concentrations of these growth factors. After treatment, the cells were counted and a western blot was performed for collagen, a-Smooth muscle actin (a-SMA), and SorlA. The total and active PAI-1 were analyzed in the NHLF supernatants. Our preliminary data show that CTGF and TGF-ß increase both total PAI-1 and SorlA expression. Data also shows an increased cell number after treatment by both growth factors. Overall, this work will help elucidate the role of PAI-1 and SorlA in scar accumulation. Studies are underway to determine the transcriptional and signaling pathways of these growth factors in lung fibroblasts, which may provide valuable information on a key therapeutic target for the treatment of IPF.
Biomedical Sciences, Interdisciplinary
