Indiana University-Purdue University Indianapolis (IUPUI) / Prostate inflammation is a common health concern as an important risk factor
for prostate cancer and Benign Prostatic Hyperplasia (BPH). Inflammation
induces epithelial apoptosis and epithelial hyperplasia, suggesting that
inflammation promotes the tissue repair and regeneration process. Progenitor
cells are critical in maintaining epithelial homeostasis in adult tissues. However,
the roles of prostate progenitor cells, especially during prostate inflammation, are
understudied. I proposed that prostate epithelial progenitor cells (PEPCs) are
involved in inflammation-induced epithelial hyperplasia, and are driven by
regulation from inflammatory pathways.
Here, we showed that sphere formation ability of prostate epithelial cells is
increased by inflammation. We identified that a population of prostate progenitor
cells, named prostate epithelial progenitor cells, were expanded by inflammation
under the regulation of IL-1/insulin-like growth factor 1 (IGF-1) signaling pathway,
a previously identified critical regulation pathway of inflammation-induced epithelial hyperplasia. The expansion of PEPCs also correlated with the intensity of inflammation.
We then identified that survivin was upregulated in prostate epithelial cells by
inflammation and was mainly co-localized with proliferation markers in prostate
epithelial cells. This upregulation depended on IL-1/IGF-1 signaling. In vivo
treatment with the survivin inhibitor LQZ-7F reduced both survivin expression and
proliferation in prostate epithelial cells during inflammation. Using our label
retaining strategy, we compared the survivin expression pattern in two prostate
regeneration models. We discovered that different populations of progenitor cells
may be involved in different regeneration processes. We identified that survivin
was expressed in a specific population of reactivated cells that respond to the
inflammatory environment and was independent of the known slow-cycling stem
cells found in the prostate epithelium. In summary, I have identified that PEPCs
are involved in epithelial hyperplasia and are dependent on survivin signaling. My
work defines how survivin serves as a key regulator of epithelial hyperplasia in
an inflammatory environment.
| Identifer | oai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/12086 |
| Date | 06 September 2016 |
| Creators | Wang, Liang |
| Contributors | Jerde, Travis, Safa, Ahmad, Srour, Edward F., Zhang, Jian-ting, Lu, Tao |
| Source Sets | Indiana University-Purdue University Indianapolis |
| Language | en_US |
| Detected Language | English |
| Type | Dissertation |
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