Distribution and isoforms of epimorphin in carbon tetrachloride-induced acute liver injury in mice.

BACKGROUND AND AIM: Epimorphin, a morphoregulatory factor essential to organ development, is believed to direct normal morphogenesis in tissue repair. We examined the dynamics and the roles of epimorphin, a cell surface-associated molecule detected on mesenchymal cells, in hepatic tissue repair from acute liver injury.

METHODS

After acute liver injury was induced by carbon tetrachloride in Balb/c mice, the distribution of epimorphin-expressing cells was studied immunohistochemically. To clarify interactions between epimorphin expression and hepatocyte behavior, epimorphin-expressing cells and proliferating hepatocytes were counted. Then, epimorphin quantity and isoforms were assessed by western blotting. To better understand effects of epimorphin, we cultured rat hepatocytes in its presence.

RESULTS

Epimorphin was distributed in relation to sinusoids, portal veins, central veins and granulomas, expressed in stellate cells and myofibroblasts. In the periportal zone, the expression in sinusoids was decreased at 24 h but increased on day 7 after carbon tetrachloride administration. Numbers of epimorphin-expressing cells and proliferating hepatocytes changed in an inverse manner as time progressed. In the pericentral zone, reactivity for epimorphin was markedly enhanced concurrently with appearance of granulomas. Quantities of 34-kDa isoform paralleled epimorphin-staining intensity. In vitro, epimorphin induced spherical hepatocyte aggregates and maintained differentiated hepatocyte function.

CONCLUSIONS

Epimorphin is involved in tissue repair following a single injection of carbon tetrachloride, in which distribution and the quantity of epimorphin expression are important, particularly in maintaining hepatocyte function.