dc.creator | Petersen, Christine Pope | |
dc.date.accessioned | 2020-08-21T21:12:47Z | |
dc.date.available | 2018-03-30 | |
dc.date.issued | 2016-03-30 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-03172016-151927 | |
dc.identifier.uri | http://hdl.handle.net/1803/10842 | |
dc.description.abstract | Spasmolytic polypeptide-expression metaplasia (SPEM) develops in the atrophic stomach and progresses to an intestinalized SPEM in the setting of inflammation. Different immune deficient mouse models determined that T-cells, B-cells, IFN gamma and neutrophils are not essential for the progression to an intestinalized SPEM. However, studies using macrophage-depleted mice found that specifically M2 macrophages were necessary for SPEM to become intestinalized. Efforts to understand macrophage-derived factors that promote the advancement of metaplasia led to RNA-sequencing of gastric macrophages in the setting of SPEM and intestinalized SPEM. A novel profile of activated gastric macrophages revealed that IL-33 is significantly upregulated in the setting of intestinalized SPEM. Inducing parietal cell loss in IL33 knock out mice uncovered an essential role for IL-33 in the transdifferentiation of mature chief cells into SPEM cells. Furthermore, IL-33 is required for the polarization of recruited macrophages towards M2a. Thus establishing a vital role for IL-33 in the development of metaplasia and macrophage polarization in response to acute parietal cell loss in the stomach. | |
dc.format.mimetype | application/pdf | |
dc.subject | cytokines | |
dc.subject | metaplasia | |
dc.subject | inflammation | |
dc.subject | gastric | |
dc.subject | stomach | |
dc.subject | M2 macrophages | |
dc.subject | macrophages | |
dc.subject | SPEM | |
dc.title | Inflammatory Mediators promote the development and progression of metaplasia in the stomach | |
dc.type | dissertation | |
dc.contributor.committeeMember | Chin Chiang | |
dc.contributor.committeeMember | Barbara Fingleton | |
dc.contributor.committeeMember | Robert Coffey | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Cell and Developmental Biology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2018-03-30 | |
local.embargo.lift | 2018-03-30 | |
dc.contributor.committeeChair | David Bader | |
dc.contributor.committeeChair | James Goldenring | |