Targeting RNA-binding protein HuR as a therapeutic strategy for mesenchymal cell proliferation and migration driven by CD4+ Th2 cytokines
Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B659
Abstract ID: 6047
Presenting Author:
Ulus Atasoy , Principal Investigator at Univ. of Michigan Med. Sch., Veterans Affairs Ann Arbor Healthcare System
Abstract:
Asthma poses significant challenges due to the airway remodeling processes, with lung fibrosis and increased airway thickness playing pivotal roles in treatment resistance. The RNA-binding protein HuR (Elavl1) has emerged as a crucial contributor to fibrosis development, regulating molecular mechanisms through post-transcriptional control of fibrotic mediators. Previous data from our research highlighted HuR's role in CD4+ Th2 cytokine expression regulation in human asthma. We hypothesized that HuR governs fibrosis induced by CD4+ Th2 cytokines in lung mesenchymal cells during allergic asthma.
In this study, human lung mesenchymal cell lines treated with Th2 cytokines (IL-13 and IL-4) exhibited elevated expression of fibrous target proteins involved in airway remodeling. Pre-treatment with a novel small molecule HuR inhibitor, KH-3, resulted in a substantial decrease in fibrotic responses. KH-3 further demonstrated a significant inhibitory effect on mesenchymal cell proliferation and disrupted lymphocyte migration in a co-culture experiment utilizing the Boyden chamber system.
These findings underscore the therapeutic potential of targeting HuR in mitigating Th2 cytokine-induced fibrosis in lung mesenchymal cells associated with airway remodeling in chronic allergic asthma. This study establishes a foundation for future therapeutic strategies targeting HuR to address airway remodeling processes which play significant roles in allergic asthma
Targeting RNA-binding protein HuR as a therapeutic strategy for mesenchymal cell proliferation and migration driven by CD4+ Th2 cytokines
Category
Poster and Podium (Block Symposium)