Distribution and isoforms of epimorphin in carbon tetrachloride-induced acute liver injury in mice.
OBJECTIVE
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.
Segawa
Daisuke
D
Department of Gastroenterology, Akita University School of Medicine, Akita, Japan.
Miura
Kouichi
K
Goto
Takashi
T
Ohshima
Shigetoshi
S
Mikami
Ken-Ichiro
K
Yoneyama
Kazuo
K
Shibuya
Tomomi
T
Watanabe
Daisuke
D
Kataoka
Ei
E
Yoshino
Ryutaro
R
Watanabe
Sumio
S
D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015153:Blotting, Western; D002251:Carbon Tetrachloride; D002449:Cell Aggregation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008115:Liver Regeneration; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D020033:Protein Isoforms / Q000378:metabolism; D014018:Tissue Distribution
C504582:Epim protein, mouse; D008562:Membrane Glycoproteins; D020033:Protein Isoforms; D002251:Carbon Tetrachloride; D000410:Alanine Transaminase