Ursodeoxycholate inhibits mast cell activation and reverses biliary injury and fibrosis in Mdr2-/- mice and human primary sclerosing cholangitis

Laboratory Investigation; a Journal of Technical Methods and Pathology
Fanyin MengHeather Francis

Abstract

Ursodeoxycholic acid (UDCA) is used to treat biliary disorders; and, bile acids alter mast cell (MC) histamine release. MCs infiltrate Mdr2-/- mice liver (model of primary sclerosing cholangitis (PSC)). MC-derived histamine increases inflammation, hepatic stellate cell (HSC) activation and fibrosis. The objective was to determine the effects of UDCA treatment on MC infiltration, biliary damage, inflammation and fibrosis in Mdr2-/- mice and human PSC. Wild-type and Mdr2-/- mice were fed bile acid control diet or UDCA (0.5% wt/wt). Human samples were collected from control and PSC patients treated with placebo or UDCA (15 mg/kg/BW). MC infiltration was measured by immunhistochemistry and quantitative polymerase chain reaction (qPCR) for c-Kit, chymase, and tryptase. The HDC/histamine/histamine receptor (HR)-axis was evaluated by EIA and qPCR. Intrahepatic bile duct mass (IBDM) and biliary proliferation was evaluated by CK-19 and Ki-67 staining. Fibrosis was detected by immunostaining and qPCR for fibrotic markers. Inflammatory components were measured by qPCR. HSC activation was measured by SYP-9 staining. Inflammation was detected by qPCR for CD68. In vitro, MCs were treated with UDCA (40 μM) prior to HA secretion evaluation and...Continue Reading

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Citations

Apr 17, 2019·Expert Opinion on Therapeutic Targets·Keisaku SatoGianfranco Alpini
Jan 22, 2020·Journal of Periodontology·Reza TalebianReinhard Gruber
Feb 18, 2020·Frontiers in Medicine·Vik MeadowsHeather Francis
Feb 11, 2020·Frontiers in Medicine·Claudio PintoMarco Marzioni
Oct 1, 2020·Scientific Reports·Anca D PetrescuSharon DeMorrow
Sep 12, 2019·American Journal of Physiology. Gastrointestinal and Liver Physiology·Stephen J KeelyNatalia K Lajczak-McGinley
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Jul 31, 2020·Gene Expression·Debjyoti KunduHeather Francis
Aug 8, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Konstantina KyritsiHeather Francis
Mar 7, 2020·The American Journal of Pathology·Lindsey KennedyHeather Francis
Jun 25, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Vik MeadowsHeather Francis
Aug 27, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Linh PhamHeather Francis

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Methods Mentioned

BETA
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