Prospero-related homeobox 1 (Prox1) is a stable hepatocyte marker during liver development, injury and regeneration, and is absent from "oval cells".
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 alpha-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.
Dudas
Jozsef
J
Department of Internal Medicine, Section of Gastroenterology and Endocrinology, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37075 Goettingen, Germany.
Elmaouhoub
Abderrahim
A
Mansuroglu
Tümen
T
Batusic
Danko
D
Tron
Kyrylo
K
Saile
Bernhard
B
Papoutsi
Maria
M
Pieler
Tomas
T
Wilting
Joerg
J
Ramadori
Giuliano
G
D015073:2-Acetylaminofluorene; D000210:Acute-Phase Reaction / Q000378:metabolism; D000818:Animals; D001652:Bile Ducts / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D022781:Hepatocytes / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D053539:Keratin-19 / Q000096:biosynthesis; D053552:Keratin-7 / Q000096:biosynthesis; D008099:Liver / Q000196:embryology* / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D000509:alpha-Fetoproteins / Q000096:biosynthesis; D000098551:Prospero-Related Homeobox 1 Protein
D015415:Biomarkers; D018398:Homeodomain Proteins; D053539:Keratin-19; D053552:Keratin-7; D025521:Tumor Suppressor Proteins; D000509:alpha-Fetoproteins; D000098551:Prospero-Related Homeobox 1 Protein; D015073:2-Acetylaminofluorene