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• W2016072676 abstract "Background: Primary sclerosing cholangitis (PSC) is associated with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. As proof of concept that CFTR dysfunction plays a role in PSC, induction of colitis in cftr−/− mice results in bile duct injury that can be prevented by pretreatment with docosahexaenoic acid (DHA). Objectives: Determine whether 1) CFTR dysfunction in cftr−/− mice through a reduction in peroxisome proliferator activated receptor (PPAR)α or γ leads to bile duct injury and 2) whether DHA prevents bile duct injury through an increase in PPAR. Methods: Cftr−/− and wild-type (WT) mice were treated with dextran sodium sulfate (DSS) to induce colitis with or without pretreatment with oral DHA. PPARα and γ as well as tumor necrosis factor (TNF)α were analyzed in liver tissue. PPARα−/− mice were also treated with DSS and histology examined. Results: PPARγ mRNA levels were low, with DSS suppressing mRNA levels equally in WT and cftr−/− mice. PPARα levels were no different between cftr−/− and WT litter mates by reverse-transcription polymerase chain reaction. After DSS, WT mice showed a 9.3-fold increase in PPARα mRNA levels and increased nuclear localization compared with no DSS (P < 0.05), with no increase seen in cftr−/− mice. This was not caused by changes in TNFα. DHA treatment led to 7.0-fold increase in PPARα mRNA levels in cftr−/− mice (P < 0.01). PPARα−/− mice treated with DSS did not develop bile duct injury, indicating that PPARα alone is not sufficient to cause bile duct inflammation. Conclusion: DSS induced bile duct injury in cftr−/− mice is associated with a defect in PPARα expression, which is reversed by DHA." @default.
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• W2016072676 date "2006-03-01" @default.
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• W2016072676 title "Decreased Peroxisome Proliferator Activated Receptor α Is Associated with Bile Duct Injury in Cystic Fibrosis Transmembrane Conductance Regulator−/− Mice" @default.
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• W2016072676 doi "https://doi.org/10.1097/01.mpg.0000189368.37535.42" @default.
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