Ming, Yanan and Zhu, Xingya and Tuma-Kellner, Sabine and Ganzha, Alexandra and Liebisch, Gerhard and Gan-Schreier, Hongying and Chamulitrat, Walee (2019) iPla2 beta Deficiency Suppresses Hepatic ER UPR, Fxr, and Phospholipids in Mice Fed with MCD Diet, Resulting in Exacerbated Hepatic Bile Acids and Biliary Cell Proliferation. CELLS, 8 (8): 879. ISSN , 2073-4409
Full text not available from this repository. (Request a copy)Abstract
Background: Group VIA calcium-independent phospholipase A2 (iPla2 beta) regulates homeostasis and remodeling of phospholipids (PL). We previously showed that iPla2 beta(-/-) mice fed with a methionine-choline-deficient diet (MCD) exhibited exaggerated liver fibrosis. As iPla2 beta is located in the endoplasmic reticulum (ER), we investigated the mechanisms for this by focusing on hepatic ER unfolded protein response (UPR), ER PL, and enterohepatic bile acids (BA). Methods: Female WT (wild-type) and iPla2 beta(-/-) mice were fed with chow or MCD for 5 weeks. PL and BA profiles were measured by liquid chromatography-mass spectrometry. Gene expression analyses were performed. Results: MCD feeding of WT mice caused a decrease of ER PL subclasses, which were further decreased by iPla2 beta deficiency. This deficiency alone or combined with MCD downregulated the expression of liver ER UPR proteins and farnesoid X-activated receptor. The downregulation under MCD was concomitant with an elevation of BA in the liver and peripheral blood and an increase of biliary epithelial cell proliferation measured by cytokeratin 19. Conclusion: iPla2 beta deficiency combined with MCD severely disturbed ER PL composition and caused inactivation of UPR, leading to downregulated Fxr, exacerbated BA, and ductular proliferation. Our study provides insights into iPla2 beta inactivation for injury susceptibility under normal conditions and liver fibrosis and cholangiopathies during MCD feeding.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FATTY LIVER-DISEASE; ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; NUCLEAR RECEPTOR FXR; TRANSPORTER EXPRESSION; LIPID DISEQUILIBRIUM; STELLATE CELLS; MEMBRANE; STEATOSIS; STEATOHEPATITIS; PLA2G6; endoplasmic reticulum; phospholipids; bile acids; lean NASH; unfolded protein response |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Apr 2020 09:48 |
| Last Modified: | 01 Apr 2020 09:48 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26488 |
Actions (login required)
 |
View Item |
