A New Xenobiotic-Induced Mouse Model of Sclerosing Cholangitis and Biliary Fibrosis

Fickert, Peter; Stöger, Ulrike; Fuchsbichler, Andrea; Moustafa, Tarek; Marschall, Hanns‐Ulrich; Weiglein, Andreas; Tsybrovskyy, Oleksiy; Jaeschke, Hartmut; Zatloukal, Kurt; Denk, Helmut; Trauner, Michael

doi:10.2353/ajpath.2007.061133

Cited by 323 publications

(360 citation statements)

References 23 publications

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“…In order to induce liver injury and Foxl1 expression, Foxl1-Cre; RosaYFP mice were fed a DDC-supplemented diet. DDC inhibits protoheme ferro-lyase activity, resulting in accumulation of protoporphyrin in hepatocytes, eventually leading to a ductular reaction and cholangitis (Tephly et al 1979;Fickert et al 2007). Treatment with DDC has been reported to induce proliferation of bipotent progenitor cells ).…”

Section: Resultsmentioning

confidence: 99%

Foxl1-Cre-marked adult hepatic progenitors have clonogenic and bilineage differentiation potential

et al. 2011

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Isolation of hepatic progenitor cells is a promising approach for cell replacement therapy of chronic liver disease. The winged helix transcription factor Foxl1 is a marker for progenitor cells and their descendants in the mouse liver in vivo. Here, we purify progenitor cells from Foxl1-Cre; RosaYFP mice and evaluate their proliferative and differentiation potential in vitro. Treatment of Foxl1-Cre; RosaYFP mice with a 3,5-diethoxycarbonyl-1, 4-dihydrocollidine diet led to an increase of the percentage of YFP-labeled Foxl1 + cells. Clonogenic assays demonstrated that up to 3.6% of Foxl1 + cells had proliferative potential. Foxl1 + cells differentiated into cholangiocytes and hepatocytes in vitro, depending on the culture condition employed. Microarray analyses indicated that Foxl1 + cells express stem cell markers such as Prom1 as well as differentiation markers such as Ck19 and Hnf4a. Thus, the Foxl1-Cre; RosaYFP model allows for easy isolation of adult hepatic progenitor cells that can be expanded and differentiated in culture.

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Section: Resultsmentioning

confidence: 99%

Foxl1-Cre-marked adult hepatic progenitors have clonogenic and bilineage differentiation potential

et al. 2011

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“…The model was recently characterized in several mouse strains, 35 and is especially attractive because it can be applied in genetically modified mice.…”

Section: Animal Modelsmentioning

confidence: 99%

Targeting Liver Fibrosis

2009

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We have made striking progress in our understanding of the biochemistry and cell biology that underlies liver fibrosis and cirrhosis, including the development of strategies and agents to prevent and reverse fibrosis. However, translation of this knowledge into clinical practice has been hampered by (1) the limitation of many in vitro and in vivo models to confirm mechanisms and to test antifibrotic agents, and (2) the lack of sensitive methodologies to quantify the degree of liver fibrosis and the dynamics of fibrosis progression or reversal in patients. Furthermore, whereas cirrhosis and subsequent decompensation are accepted hard clinical endpoints, fibrosis and fibrosis progression alone are merely plausible surrogates for future clinical deterioration. In this review we focus on an optimized strategy for preclinical antifibrotic drug development and highlight the current and future techniques that permit noninvasive assessment and quantification of liver fibrosis and fibrogenesis. The availability of such noninvasive methodologies will serve as the pacemaker for the clinical development and validation of potent antifibrotic agents. (HEPATOLOGY 2009;50:1294-1306

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“…Another nonsurgical model where obstruction of bile ducts and proliferation of cholangiocytes occur is based on dietary model using 3,5-diethoxycarbonyl-1,4-dihydrocollidine-enriched diet. 33 In this model, porphyrin crystals block small intrahepatic bile ducts and large bile ducts remain usually unaffected.…”

Section: Models To Target Cholangiocytesmentioning

confidence: 99%

Metalloproteinases in liver fibrosis: current insights

Zbodakova¹,

Chalupský²,

Turečková³

et al. 2017

MNM

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Liver fibrosis is defined by excessive deposition of extracellular matrix. The fibrotic conditions result from the imbalance between synthesis and deposition of fibrous tissues and decomposition of these matrix proteins. This process can be reversed as a regular part of the healing process after hepatic damage or can become chronic. When the protein matrix synthesis predominates and the decomposition is suppressed, fibrosis will progress into irreversible cirrhosis or steatosis. Among the molecular players involved in fibrotic liver diseases, metalloproteinases of matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase (ADAM) families are critical in the development of liver fibrosis and its resolution. Previously, MMPs were recognized as extracellular matrix degrading enzymes. Currently, they are also known as mediators in a variety of processes related to immunity and tissue repair. In this article, we have reviewed the models of liver fibrosis and findings on MMPs and ADAMs in hepatic fibrosis conditions.

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A New Xenobiotic-Induced Mouse Model of Sclerosing Cholangitis and Biliary Fibrosis

Cited by 323 publications

References 23 publications

Foxl1-Cre-marked adult hepatic progenitors have clonogenic and bilineage differentiation potential

Foxl1-Cre-marked adult hepatic progenitors have clonogenic and bilineage differentiation potential

Targeting Liver Fibrosis

Metalloproteinases in liver fibrosis: current insights

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