Date of Award

12-31-2017

Document Type

Campus Access Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Jill A. Macoska

Second Advisor

Alexey Veraksa

Third Advisor

Todd Riley

Abstract

Lower urinary tract symptoms (LUTS) comprise a number of medical conditions including weak stream, incomplete bladder voiding, and nocturia that affect quality of life and can progress to more severe symptoms if left untreated. Treatments for LUTS typically target overproliferation caused by benign prostate hyperplasia (BPH) and smooth muscle dysfunction, although these approaches do not always alleviate symptoms. Recent studies have shown that fibrosis may also play an important role in the development of LUTS. Fibrosis is an errant wound healing process that occurs in response to chronic inflammation and is driven at the cellular level by differentiation of fibroblasts and other precursor cell types into myofibroblasts. While the TGFβ signaling pathway is typically regarded as the canonical driver of myofibroblast phenoconversion, our lab has shown that several CXC-type chemokines that are upregulated in the aging prostate, namely CXCL5, CXCL8, and CXC12, are capable of promoting myofibroblast phenoconversion in prostate stromal fibroblasts in the absence of TGFβ signaling. The mechanism that mediates CXCL5-induced myofibroblast phenoconversion, however, is currently unknown, and therefore I sought to determine the identity of the signaling pathway(s) downstream of the CXCL5/CXCR2 axis that promote myofibroblast phenoconversion. The results suggest that CXCL5 mediates myofibroblast phenoconversion through EGFR transactivation followed by downstream MEK/ERK signaling, independent of TGFβ pathway signaling.

Comments

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