Differential expression of CD44 isoforms during liver regeneration in rats.
BACKGROUND
CD44 is a transmembrane glycoprotein known to bind hyaluronic acid (HA). This molecule is a multifunctional cell surface glycoprotein involved in lymphocyte homing and activation, tumor growth and metastasis. We have investigated the qualitative modification of CD44 in the regenerating liver as a model for studying cellular proliferation in vivo. Molecules involved in cell adhesion and the extracellular matrix (ECM), which influence differentiation, growth, cell-cell interactions and cellular polarity, play an important role in the liver regeneration. We studied the modulation of CD44 gene expression and its post-transcriptional modifications, analyzing the expression of different isoforms containing exon v6 in the regenerating liver, in sham operated liver and in the hepatoma cells H-35.


METHODS
The expression of CD44 and CD44v6 were analyzed in RNA extracted from regenerating liver at different times after partial hepatectomy (PH), and H-35 hepatoma cells by Northern blot, RT-PCR and Southern blot, and in protein extracts from regenerating liver by Western blot. H-35 hepatoma cells were assayed with the antibody cross-linked technique with CD44 antibodies.


RESULTS
The standard CD44 form is expressed in regenerating liver and its levels were not modified following PH. However, our analysis revealed CD44 isoforms containing v6 in the first hours after PH as well as in the H-35 hepatoma cell line. H-35 cells treated with cross-linked anti-CD44 antibodies or HA show an increased rate of incorporation of [3H]thymidine (30 and 25%, respectively) with respect to the control.


CONCLUSIONS
These findings suggest that CD44 may play a role in the proliferation of residual hepatocytes following PH.
Della Fazia
M A
MA
Dipartimento di Scienze Biochimiche e di Biotecnologie Molecolari, Università di Perugia, Policlinico Monteluce, Italy.
Pettirossi
V
V
Ayroldi
E
E
Riccardi
C
C
Magni
M V
MV
Servillo
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000166:cytology; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors; D020033:Protein Isoforms