Oval cell (OvCs) involvement in regeneration is a well known phenomenon in models of liver injury, however, the activation of these cells following streptozotocin (STZ)-induced diabetes has not been studied yet. Differentiation of liver cells toward insulin-producing cells in diabetes has been reported, but the cell phenotype is still unclear. The aim of the present study was to confirm by immunohistochemical analysis, the activation of OvCs and their ability to express pancreatic beta-cell phenotype in STZ-induced diabetic mice. Using specific anti-A6 antibodies for mouse OvCs, we found a three-fold increase in periportal number and two-fold higher density of OvCs in diabetic livers, when compared to controls. Unlike non-diabetic controls, double staining technique showed co-localization of A6 and proinsulin in the cytoplasm of OvCs of diabetic animals, but no insulin staining was detected, probably reflecting the premature character of OvCs differentiation toward beta-cell-like phenotype. These data add valuable information concerning the nature and the stage of functional maturity of liver cells undergoing differentiation toward beta-cell phenotype in STZ-induced diabetic animals.
Diabetes Hepatic oval cells A6 antigen Proinsulin
This is a preview of subscription content, log in to check access
The authors thank Dr. Valentina Factor (National Institute of Health, USA) for kindly providing antibodies to A6 antigen and Sara Dominitz for editorial help. This work was supported in part by a grant from the Research Foundation of Tel Aviv University (#0601563121). MV is a recipient of a scholarship from the Legacy Heritage Fund, Developmental and Cell Biology Department, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Jelnes P, Santoni-Rugiu E, Rasmussen M et al (2007) Remarkable heterogeneity displayed by oval cells in rat and mouse models of stem cell-mediated liver regeneration. Hepatology 45:1462–1470. doi:10.1002/hep.21569PubMedCrossRefGoogle Scholar
Kim S, Shin J, Kim H et al (2007) Streptozotocin-induced diabetes can be reversed by hepatic oval cell activation through hepatic transdifferentiation and pancreatic islet regeneration. Lab Invest 87:702–712. doi:10.1038/labinvest.3700561PubMedCrossRefGoogle Scholar
Okamoto H, Takasawa S (2002) Recent advances in the Okamoto model: the CD38-cyclic ADP-ribose signal system and the regenerating gene protein (Reg)-Reg receptor system in beta-cells. Diabetes 51:462–473. doi:10.2337/diabetes.51.2007.S462CrossRefGoogle Scholar
Rhee S, Jeong Y, Choi J (2005) Effects of vitamin E on phospholipase A 2 activity and oxidative damage to the liver in streptozotocin-induced diabetic rats. Ann Nutr Metab 49:392–396. doi:10.1159/000088930PubMedCrossRefGoogle Scholar