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Prospero-related homeobox 1 (Prox1) is a stable hepatocyte marker during liver development, injury and regeneration, and is absent from “oval cells”

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Abstract

The aim of this study was to analyse the changes of Prospero-related homeobox 1 (Prox1) gene expression in rat liver under different experimental conditions of liver injury, regeneration and acute phase reaction, and to correlate it with that of markers for hepatoblasts, hepatocytes, cholangiocytes and oval cells. Gene expression was studied at RNA level by RT-PCR, and at protein level by immunohistochemistry. At embryonal stage of rat liver development (embryonal days (ED) 14–16) hepatoblasts were found to be Prox1+/Cytokeratin (CK) 19+ and α-fetoprotein (AFP)+, at this stage Prox1−/CK19+/AFP- small cells (early cholangiocytes?) were identified. In fetal liver (ED 18–22) hepatoblasts were Prox1+/CK19−/AFP+. CK7+ cholangiocytes were detected at this stage, and they were Prox1−/AFP−. In the adult liver hepatocytes were Prox1+/CK19−/CK7−/AFP−, cholangiocytes were CK19+ and/or CK7+ and AFP−/Prox1−. In models of liver damage and regeneration Prox1 remained a stable marker of hepatocytes. After 2-acetyl-aminofluorene treatment with partial hepatectomy (AAF/PH) the amount of Prox1 specific transcripts was low in the liver, when CK19 and AFP gene expression was high, and at no time point AFP+/CK19+ “oval cells” were found to be Prox1+. However, a few Prox1+/CK19+ and a few Prox1+/CK7+ cells were identified in the liver of AAF/PH-animals, which may represent precursors of hepatocytes, or a precancerous state.

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Acknowledgments

We are grateful to Mrs. Ch. Hoffmann, Mrs. A. Herbst and Mrs. S. Georgi for their excellent technical assistance. We greatly appreciate the help of Dr. Sabine Blascke, Department of Internal Medicine, Section of Nephrology, Georg-August-University Goettingen, Germany, during the laser capture experiments. This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB 402, projects C6, D3, D4).

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Authors and Affiliations

  1. Department of Internal Medicine, Section of Gastroenterology and Endocrinology, Georg-August-University Göttingen, Robert-Koch-Straße 40, 37075, Goettingen, Germany

    Jozsef Dudas, Abderrahim Elmaouhoub, Tümen Mansuroglu, Danko Batusic, Kyrylo Tron, Bernhard Saile & Giuliano Ramadori

  2. Pediatrics I, Children’s Hospital, Georg-August-University, Goettingen, Germany

    Maria Papoutsi & Joerg Wilting

  3. Department of Developmental Biochemistry, Institute of Biochemistry and Molecular Cell Biology, Georg-August-University, Goettingen, Germany

    Tomas Pieler

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  1. Jozsef Dudas
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  2. Abderrahim Elmaouhoub
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  3. Tümen Mansuroglu
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  4. Danko Batusic
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  5. Kyrylo Tron
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  6. Bernhard Saile
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  10. Giuliano Ramadori
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Correspondence to Giuliano Ramadori.

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Dudas, J., Elmaouhoub, A., Mansuroglu, T. et al. Prospero-related homeobox 1 (Prox1) is a stable hepatocyte marker during liver development, injury and regeneration, and is absent from “oval cells” . Histochem Cell Biol 126, 549–562 (2006). https://doi.org/10.1007/s00418-006-0191-4

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