Characterization of the erythropoietin/erythropoietin receptor axis in a rat model of liver damage and cholangiocarcinoma development

摘要: It has been recently shown that the biological effects of erythropoietin (EPO) are not limited to hematopoietic compartment but, as pleiotropic glycoprotein, this hormone can exert pro-angiogenic and tissue-protective functions also in a wide range non-hematopoietic organs. The role EPO effective functionality its receptor solid tumors still controversial point debate. In present work we analyzed gene expression cognate (EpoR) rat model thioacetamide-induced damage tumor. An analysis EPO/EpoR axis was performed on human cholangiocarcinoma (CC) cell lines. A progressive increase EpoR mRNA already be observed during fibrotic–cirrhotic development with peak rising at tumor formation (24.7 ± 9.9-fold 15.5 1.1-fold increase, respectively, for two genes). Co-localization studies by immunofluorescence revealed hepatocytes regenerative cirrhotic nodules (Hep Par-1+) dysplastic bile duct cells (CK19+) major producers specific condition. same populations, together endothelial cells, exhibited an increased EpoR, although all non-parenchymal populations liver modest basal levels. Challenging CC Mz-Cha-2, combination SCF resulted synergistic effect EPO, CyclinD1 PCNA. This study suggests autocrine paracrine release endogenous microenvironment may contribute maintenance possibly cooperation other signaling pathways.