1 40 1 Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. URL Address <a href="http://doi.org/10.1194/jlr.M044420" target="_blank" rel="noreferrer noopener">http://doi.org/10.1194/jlr.M044420</a> Rights Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s). Pages 455-465 Issue 3 Volume 55 Search for Full-text Locate full-text within NEOMED Library's e-journal collections <p>Users with a NEOMED Library login can search for full-text journal articles at the following url: <a href="https://libraryguides.neomed.edu/home">https://libraryguides.neomed.edu/home</a></p> Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Intestinal CYP3A4 protects against lithocholic acid-induced hepatotoxicity in intestine-specific VDR-deficient mice Publisher An entity responsible for making the resource available Journal of Lipid Research Date A point or period of time associated with an event in the lifecycle of the resource 2014 2014-03 Subject The topic of the resource metabolomics; 1; Biochemistry & Molecular Biology; disease; expression; absorption; permeability; Bile acids; bile-acid; cytochrome-p450 3a4; vitamin D receptor; vitamin D receptor; 25-dihydroxyvitamin d-3 Creator An entity primarily responsible for making the resource Cheng J; Fang Z Z; Kim J H; Krausz K W; Tanaka N; Chiang J Y L; Gonzalez F J Description An account of the resource Vitamin D receptor (VDR) mediates vitamin D signaling involved in bone metabolism, cellular growth and differentiation, cardiovascular function, and bile acid regulation. Mice with an intestine-specific disruption of VDR (Vdr(Delta IEpC)) have abnormal body size, colon structure, and imbalance of bile acid metabolism. Lithocholic acid (LCA), a secondary bile acid that activates VDR, is among the most toxic of the bile acids that when overaccumulated in the liver causes hepatotoxicity. Because cytochrome P450 3A4 (CYP3A4) is a target gene of VDR-involved bile acid metabolism, the role of CYP3A4 in VDR biology and bile acid metabolism was investigated. The CYP3A4 gene was inserted into Vdr(Delta IEpC) mice to produce the Vdr(Delta IEpC)/3A4 line. LCA was administered to control, transgenic-CYP3A4, Vdr(Delta IEpC), and Vdr(Delta IEpC)/3A4 mice, and hepatic toxicity and bile acid levels in the liver, intestine, bile, and urine were measured. VDR deficiency in the intestine of the Vdr(Delta IEpC) mice exacerbates LCA-induced hepatotoxicity manifested by increased necrosis and inflammation, due in part to over-accumulation of hepatic bile acids including taurocholic acid and taurodeoxycholic acid. Intestinal expression of CYP3A4 in the Vdr(Delta IEpC)/3A4 mouse line reduces LCA-induced hepatotoxicity through elevation of LCA metabolism and detoxification, and suppression of bile acid transporter expression in the small intestine.(jlr) This study reveals that intestinal CYP3A4 protects against LCA hepatotoxicity. Identifier An unambiguous reference to the resource within a given context <a href="http://doi.org/10.1194/jlr.M044420" target="_blank" rel="noreferrer noopener">10.1194/jlr.M044420</a> Format The file format, physical medium, or dimensions of the resource Journal Article or Conference Abstract Publication 1 2014 25-dihydroxyvitamin d-3 Absorption BILE acids bile-acid Biochemistry & Molecular Biology Cheng J Chiang J Y L cytochrome-p450 3a4 Disease expression Fang Z Z Gonzalez F J Journal Article or Conference Abstract Publication Journal of lipid research Kim J H Krausz K W Metabolomics Permeability Tanaka N vitamin D receptor