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Downregulation of intestinal Farnesoid X Receptor in Erythropoietic protoporphyria

Pradhan, Komal (2017) Downregulation of intestinal Farnesoid X Receptor in Erythropoietic protoporphyria. Master's Thesis, University of Pittsburgh. (Unpublished)

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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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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Pradhan, Komalkdp29@pitt.edukdp29
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorMa, XiaochaoMXIAOCHA@pitt.eduMXIAOCHA
Committee MemberYang, Dadyang@pitt.edudyang
Sant, VinayakVIS45@pitt.eduVIS45
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


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