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

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 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.

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

“…Other markers of the progenitor compartment-such as Cldn3, Ncam1, Dlk1, and Onecut2-are enriched in the YFP + population only at day 14, indicating that previously reported markers can be classified to early markers and later markers (Schmelzer et al 2006;Snykers et al 2009;Tanaka et al 2009). In addition, YFP + cells were enriched for cholangiocyte markers Ck19 (Krt19), Ck7 (Krt7), Onecut1, and Hnf1b, as well as hepatocyte markers Hnf4a, Hnf1a, and Prox1 (Dudas et al 2006;data not shown (Seymour et al 2007).…”

The New Era of the Lymphatic System: No Longer Secondary to the Blood Vascular System

“…Despite a high protein sequence similarity between Prospero and Prox1, the amino acid motif responsible for this asymmetric segregation of Prospero seems not present in Prox1 , and asymmetric segregation of Prox1 has not been reported to date. Like Prospero, Prox1 is also expressed in many other organs, such as the liver, brain, pancreas, heart, eye lens, ear sensory epithelium, taste bud, and retina (Oliver et al 1993;SosaPineda et al 2000;Govindarajan and Overbeek 2001;Miura et al 2003;Bermingham-McDonogh et al 2006;Dudas et al 2006;Edqvist et al 2006;Laerm et al 2007;Kirjavainen et al 2008;Risebro et al 2009). Interestingly, the cell-fate-specifying function of Prospero seems to have been inherited by Prox1 and appears to be the common functional theme of Prox1 in such diverse cell types.…”

Thy-1 is expressed in myofibroblasts but not found in hepatic stellate cells following liver injury

“…Ubiquitin C expression was not aVected by any of the treatments used in the animal models. The normalized Thy-1, Fibulin-2, Desmin, Gremlin and SMA PCR-product quantities of treated animals were compared to the values of control animals, and the relative expression was plotted against the observation time ( Dudas et al 2006Dudas et al , 2007. In all cases, two or more animal series were analyzed in duplicates.…”