Deficiency of multidrug resistance 2 contributes to cell transformation through oxidative stress

Tebbi, Ali; Levillayer, Florence; Jouvion, Grégory; Fiette, Laurence; Soubigou, Guillaume; Varet, Hugo; Boudjadja, Nesrine; Cairo, Stefano; Hashimoto, Kosuke; Suzuki, Ana Maria; Carninci, Piero; Carissimo, Annamaria; Bernardo, Diego di; Yu, Wei

doi:10.1093/carcin/bgv156

Cited by 14 publications

(3 citation statements)

References 41 publications

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“…To integrate the IBD component, previously defined in vivo models can also be conjugated with DSS feeding. To date, three such combinational models have been described in Cftr ‐/‐ mice or Mdr2 ‐/‐ mice 127,176,200,201,204,210,211 . Administering DSS to Mdr2 ‐/‐ mice results in an exacerbated sclerosing cholangitis along with increased ductular reaction and bridging fibrosis 201 .…”

Section: Combination Modelsmentioning

confidence: 99%

“…To date, three such combinational models have been described in Cftr -/mice or Mdr2 -/mice. 127,176,200,201,204,210,211 Administering DSS to Mdr2 -/mice results in an exacerbated sclerosing cholangitis along with increased ductular reaction and bridging fibrosis. 201 Similarly, DSS can be administered to Cftr -/mice, producing a significant increase in bile duct injury compared to the phenotype observed in Cftr -/mice.…”

Section: Primary Sclerosing Cholangitismentioning

confidence: 99%

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Rodent models of cholestatic liver disease: A practical guide for translational research

Gijbels

Pieters

Muynck

et al. 2021

Liver International

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Cholestatic liver disease denotes any situation associated with impaired bile flow concomitant with a noxious bile acid accumulation in the liver and/or systemic circulation. Cholestatic liver disease can be subdivided into different types according to its clinical phenotype, such as biliary atresia, drug‐induced cholestasis, gallstone liver disease, intrahepatic cholestasis of pregnancy, primary biliary cholangitis and primary sclerosing cholangitis. Considerable effort has been devoted to elucidating underlying mechanisms of cholestatic liver injuries and explore novel therapeutic and diagnostic strategies using animal models. Animal models employed according to their appropriate applicability domain herein play a crucial role. This review provides an overview of currently available in vivo animal models, fit‐for‐purpose in modelling different types of cholestatic liver diseases. Moreover, a practical guide and workflow is provided which can be used for translational research purposes, including all advantages and disadvantages of currently available in vivo animal models.

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Section: Combination Modelsmentioning

confidence: 99%

Section: Primary Sclerosing Cholangitismentioning

confidence: 99%

Rodent models of cholestatic liver disease: A practical guide for translational research

Gijbels

Pieters

Muynck

et al. 2021

Liver International

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“…Mdr2 −/− mice are a widely used model of inflammation-induced HCC. These animals lack the multi drug resistance protein 2 (MDR2), a phosphatidylcholine transporter, resulting in dysfunctional phospholipid secretion and increased oxidative stress, which in turn leads to chronic liver damage, leukocyte infiltration, fibrosis, and over time to HCC development 4 , 5 .…”

Section: Introductionmentioning

confidence: 99%

Early heme oxygenase 1 induction delays tumour initiation and enhances DNA damage repair in liver macrophages of Mdr2−/− mice

Barikbin

Berkhout

Bolik

et al. 2018

Sci Rep

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Multi drug resistance protein 2 knockout mice (Mdr2−/−) are a mouse model of chronic liver inflammation and inflammation-induced tumour development. Here we investigated the kinetics of early heme oxygenase 1 (HO-1) induction on inflammation, tumour development, and DNA damage in Mdr2−/− mice. HO-1 was induced by intraperitoneal injection of cobalt protoporphyrin IX (CoPP) twice weekly for 9 consecutive weeks. Immediately after HO-1 induction, liver function improved and infiltration of CD4+ and CD8+ T cells was reduced. Furthermore, we observed increased p38 activation with concomitant reduction of Cyclin D1 expression in aged Mdr2−/− mice. Long-term effects of HO-1 induction included increased CD8+ T cell infiltration as well as delayed and reduced tumour growth in one-year-old animals. Unexpectedly, DNA double-strand breaks were detected predominantly in macrophages of 65-week-old Mdr2−/− mice, while DNA damage was reduced in response to early HO-1 induction in vivo and in vitro. Overall, early induction of HO-1 in Mdr2−/− mice had a beneficial short-term effect on liver function and reduced hepatic T cell accumulation. Long-term effects of early HO-1 induction were increased CD8+ T cell numbers, decreased proliferation as wells as reduced DNA damage in liver macrophages of aged animals, accompanied by delayed and reduced tumour growth.

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Gene Mutations and Its Clinical Significance

Lee

Park

2020

Diseases of the Gallbladder

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Deficiency of multidrug resistance 2 contributes to cell transformation through oxidative stress

Abstract: SummaryThe transporter of phosphatidylcholine Mdr2/MDR3 not only plays an essential role for bile formation but also is involved in the maintenance of lipid homeostasis. Deficiency of Mdr2 leads to accumulation of ROS, cell transformation and susceptibility to intestinal carcinogenesis.

Cited by 14 publications

References 41 publications

Rodent models of cholestatic liver disease: A practical guide for translational research

Rodent models of cholestatic liver disease: A practical guide for translational research

Early heme oxygenase 1 induction delays tumour initiation and enhances DNA damage repair in liver macrophages of Mdr2−/− mice

Gene Mutations and Its Clinical Significance

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