DeDionisio, Adam
(2020)
Establishing a New Model of Endotoxemia-Associated Acute Kidney Injury in Zebrafish.
Master's Thesis, University of Pittsburgh.
(Unpublished)
This is the latest version of this item.
Abstract
Sepsis is a leading cause of in-hospital patient deaths and is characterized through a systemic inflammatory response and subsequent organ failures. The kidney is known to be particularly susceptible to injury in this setting, with sepsis-associated acute kidney injury (S-AKI) being the most common organ dysfunction during sepsis. Notwithstanding this prevalence, the general mechanisms which cause S-AKI are largely unknown. Hypotheses regarding the roles of pro-inflammatory molecular pathways and related cellular responses have been of interest to explain such pathological effects. While recent studies have made strides to identify biomarkers of S-AKI from human patient data, and altered molecular pathways from animal and in vitro models, one source difficulty in making further progress are the model systems themselves. Current model systems are rife with their own complications; many fail to mirror known human S-AKI pathologies, and many are either difficult to work with, or do not give consistent results from one assay to the next. Here, we strove to develop a new in vivo model of S-AKI through microinjections of the endotoxin lipopolysaccharide from Pseudomonas aeruginosa into zebrafish larvae. While much is to be learned from this model, early data suggests this system is efficient, easy to work with, consistent, and shows hallmarks of kidney dysfunction and proinflammatory responses post-injection. As such, it may act as a valuable tool to understand the biopathology of S-AKI, as well as serve as a vital high throughput drug discovery model to identify novel therapeutics.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
4 September 2020 |
| Date Type: |
Publication |
| Defense Date: |
30 July 2020 |
| Approval Date: |
4 September 2020 |
| Submission Date: |
30 July 2020 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
51 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Molecular Genetics and Developmental Biology |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
sepsis
S-AKI
sepsis-associated acute kidney injury
zebrafish
endotoxemia
lipopolysaccharide
LPS |
| Date Deposited: |
04 Sep 2020 13:30 |
| Last Modified: |
04 Sep 2020 13:30 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/39642 |
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Establishing a New Model of Endotoxemia-Associated Acute Kidney Injury in Zebrafish. (deposited 04 Sep 2020 13:30)
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