Expression of oncostatin M and its receptors in normal and cirrhotic human liver.
OBJECTIVE
In the cirrhotic liver, gene expression of the multifunctional cytokine oncostatin M (OSM) is up-regulated, but its cellular origin is unknown. Therefore, we investigated the expression of OSM protein and its specific receptor subunits, OSMRbeta and LIFRbeta in normal and cirrhotic human liver using immunohistochemical and Western blot analysis.


RESULTS
OSM protein was expressed in Kupffer cells, variably in normal liver but consistently in cirrhosis. OSMRbeta was expressed at low level in hepatocytes of all normal livers examined, but in no cirrhotic sample. In contrast, LIFRbeta receptor was expressed weakly in normal livers, but much more intensely in cirrhosis, in reactive ductules, bile duct epithelial cells and perisinusoidal areas. Double immunostaining showed co-localization of LIFRbeta with cytokeratin 7, proliferating cell nuclear antigen (PCNA) and leukemia inhibitory factor (LIF), in bile duct epithelial cells, but not with alpha-smooth muscle actin, a myofibroblast marker.


CONCLUSIONS
In human liver, OSM protein is expressed in Kupffer cells, variably in normals but universally in cirrhosis. The differential expression pattern of OSM and its receptors could allow for differential OSM signaling by alternative utilization of receptors to promote hepatocyte proliferation in acute injury and, with its homologue LIF, for the bile ductular reaction in cirrhosis.
Znoyko
Iya
I
Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Sohara
Naondo
N
Spicer
Samuel S
SS
Trojanowska
Maria
M
Reuben
Adrian
A
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D015870:Gene Expression; D006131:Growth Inhibitors / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053552:Keratin-7; D007633:Keratins / Q000378:metabolism; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism*; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D018836:Inflammation Mediators; C507497:KRT7 protein, human; D053552:Keratin-7; C507840:LIFR protein, human; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C508351:OSM protein, human; D010455:Peptides; D021122:Protein Subunits; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; D053683:Oncostatin M; D007633:Keratins