Date of Award
8-2024
Document Type
Campus Access Thesis
Degree Name
Master of Science (MS)
Department
Biology
First Advisor
Jill A. Macoska
Second Advisor
Jonathan Celli
Third Advisor
Juliet Girard
Abstract
Lower urinary tract dysfunction (LUTD) is a persistent disease that leaves patients to face harsh symptoms such as urinary voiding dysfunction, frequent Urinary Tract Infections (UTIs), and can even progress to renal failure (Bushman et al. 2016). Our lab has discovered that prostate fibrosis contributes to LUTD, which offers a new avenue of treatment. Myofibroblasts and activated fibroblasts, major agents of fibrosis, are resistant to apoptosis, and instead persist, accumulate, and promote pathological deposition of ECM. Previous work has shown that the IL-4/IL-13 signaling axis promotes prostate fibrosis. IL-4, which is abundant in the aging prostate microenvironment, prevents apoptosis in Th2 macrophages. IL-4 has also been shown to promote fibroblast migration and proliferation in different cell lines. IL-4 and IL-13 signal transduction occurs through a shared axis, suggesting that both interleukins may play key roles in resistance to apoptosis, migration, and proliferation. We hypothesized that the IL-4/IL-13 axis may repress myo/activated fibroblast apoptosis, thereby contributing to lower urinary tract dysfunction (LUTD). In brief, a series of experiments determined that IL-4 repressed apoptosis in primary human prostate fibroblasts (pHPFs) treated with the pro-apoptotic cocktail TRIO. Fibroblasts treated with vehicle or IL-4 exhibited no caspase cleavage, low levels of cell death, and decreased FADD expression. When treated with TRIO, cells exhibited high levels of cell death and caspase cleavage/activation compared to non-TRIO treated cells. Cells pre-treated with IL-4 followed by TRIO showed significantly less caspase 3 and caspase 8 cleavage/activation and reduced levels of cell death. IL-4 also significantly upregulated the migration of pHPFs. IL-4 and IL-13 slightly increased pHPF proliferation. Future research will aim to elucidate how IL-4 is modulating FADD with the intent of inhibiting this mechanism to prevent fibroblast persistence and LUTD.
Recommended Citation
Sarna-McCarthy, Marissa, "The Effects of IL-4/IL-13 on Fibrotic Persistance in Primary Human Prostate Fibroblasts" (2024). Graduate Masters Theses. 848.
https://scholarworks.umb.edu/masters_theses/848
Comments
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