Nuclear Factor, Erythroid 2-Like 2 Regulates Expression of Type 3 Inositol 1,4,5-Trisphosphate Receptor and Calcium Signaling in Cholangiocytes

Gastroenterology
Jittima WeerachayaphornM H Nathanson

Abstract

Most cholestatic disorders are caused by defects in cholangiocytes. The type 3 isoform of the inositol 1,4,5-trisphosphate receptor (ITPR3) is the most abundant intracellular calcium release channel in cholangiocytes. ITPR3 is required for bicarbonate secretion by bile ducts, and its expression is reduced in intrahepatic bile ducts of patients with cholestatic disorders. We investigated whether the nuclear factor, erythroid 2-like 2 (NFE2L2 or NRF2), which is sensitive to oxidative stress, regulates expression of ITPR3. The activity of the ITPR3 promoter was measured in normal human cholangiocyte (NHC) cells and primary mouse cholangiocytes. Levels of ITPR3 protein and messenger RNA were examined by immunoblot and polymerase chain reaction analyses, respectively. ITPR3 activity was determined by measuring calcium signaling in normal human cholangiocyte cells and secretion in isolated bile duct units. Levels of NRF2 were measured in liver tissues from rats with cholestasis (induced by administration of α-napthylisothiocyanate) and from patients with biliary diseases. We identified a musculo-aponeurotic fibrosarcoma recognition element in the promoter of ITPR3 that bound NRF2 directly in NHC cells and mouse cholangiocytes. Increa...Continue Reading

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Citations

Apr 23, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xiao ZhaoMichael Pack
Aug 25, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Andressa FrancaMichael H Nathanson
Aug 12, 2016·Physiological Reviews·Michael J Berridge
Jun 30, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Pimwipa UeasilamongkolJittima Weerachayaphorn
Aug 17, 2016·Oncotarget·Sona HudecovaOlga Krizanova
Dec 20, 2018·International Journal of Molecular Sciences·Michele Angela RodriguesMichael Harris Nathanson
Jul 26, 2019·International Journal of Molecular Sciences·Kemper Nunes Dos SantosM Fatima Leite
Dec 6, 2019·World Journal of Gastroenterology : WJG·Fernanda de Oliveira LemosM Fatima Leite
Oct 8, 2020·World Journal of Biological Chemistry·Indiwari Gopallawa, Robert J Lee
Feb 13, 2021·Journal of Experimental & Clinical Cancer Research : CR·Mengzhao ZhangJinhai Fan
Feb 23, 2021·Journal of Hepatology·James Lorenzen Boyer, Carol Jean Soroka
Sep 18, 2021·Journal of Cell Science·Vikas ArigeDavid I Yule

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