Differential expression of CD44 isoforms during liver regeneration in rats

Background: CD44 is a transmembrane glycoprotein known to bind hyaluronic a cid (HA). This molecule is a multi-functional cell surface glycoprotein inv olved 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 inv olved 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 f rom regenerating liver at different times after partial hepatectomy (PH), a nd H-35 hepatoma cells by Northern blot, RT-PCR and Southern blot, and in p rotein extracts from regenerating liver by Western blot. H-35 hepatoma cell s were assayed with the antibody cross-linked technique with CD44 antibodie s. 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 h epatoma cell line. H-35 cells treated with cross-linked anti-CD44 antibodie s or HA show an increased rate of incorporation of [H-3]thymidine (30 and 2 5%, respectively) with respect to the control. Conclusion: These findings suggest that CD44 may play a role in the prolife ration of residual hepatocytes following PH. (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights r eserved.