Pradhan, Komal
(2017)
Downregulation of intestinal Farnesoid X Receptor in Erythropoietic protoporphyria.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Erythropoietic protoporphyria (EPP) is characterized by accumulation of protoporphyrin IX (PPIX) in the body. The liver is the major organ responsible for PPIX excretion through the biliary system. Because PPIX is highly hydrophobic, an excess amount of PPIX will precipitate in bile ducts, which can physically block bile flow and result in cholestatic liver injury. Bile acids are natural ligands of Farnesoid X Receptor (FXR) and FXR is a ligand dependent transcription factor. In EPP-associated liver injury, bile ducts are blocked by PPIX which can decrease intestinal exposure to bile acids. Therefore, we hypothesize that PPIX-mediated bile duct blockage will decrease intestinal exposure of bile acids and suppress FXR signaling pathway. By using a genetically engineered EPP mouse model, we confirmed our hypothesis by revealing that the FXR target genes including FGF15, Bsep and Shp, were significantly suppressed in the intestine. In summary, this project demonstrated that the intestinal FXR function is suppressed in EPP.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
26 April 2017 |
| Date Type: |
Publication |
| Defense Date: |
7 April 2017 |
| Approval Date: |
26 April 2017 |
| Submission Date: |
15 April 2017 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
29 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Pharmacy > Pharmaceutical Sciences |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Erythropoietic protoporphyria, FXR, cholestasis, Bsep, Shp, FGF15, LPS |
| Date Deposited: |
26 Apr 2017 16:49 |
| Last Modified: |
27 Apr 2017 05:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/31486 |
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