Vasoactive intestinal peptide induces proliferation of human hepatocytes |
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| Authors: | M E M S Khedr A M Abdelmotelb T A Bedwell A Shtaya M N Alzoubi M Abu Hilal S I Khakoo |
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| Institution: | 1. Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK;2. Faculty of Medicine, Suez Canal University, Ismailia, Egypt;3. Faculty of Medicine, Tanta University, Tanta, Egypt;4. St George's University of London, London, UK;5. University of Jordan, Amman, Jordan;6. Southampton University Hospitals NHS Trust, Southampton, UK |
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| Abstract: | Objectives Proliferation of hepatocytes in vitro can be stimulated by growth factors such as epidermal growth factor (EGF), but the role of vasoactive intestinal peptide (VIP) remains unclear. We have investigated the effect of VIP on maintenance and proliferation of human hepatocytes. Materials and methods Human hepatocytes were isolated from liver specimens obtained from patients undergoing liver surgery. Treatment with VIP or EGF was started 24 h after plating and continued for 3 or 5 d. DNA replication was investigated by Bromodeoxyuridine (BrdU) incorporation and cell viability detected by MTT assay. Cell lysate was analysed by western blotting and RT‐PCR. Urea and albumin secretion into the culture supernatants were measured. Results VIP increased DNA replication in hepatocytes in a dose‐dependant manner, with a peak response at day 3 of treatment. VIP treatment was associated with an increase in mRNA expression of antigen identified by monoclonal antibody Ki‐67 (MKI‐67) and Histone Cluster 3 (H3) genes. Western blotting analysis showed that VIP can induce a PKA/B‐Raf dependant phosphorylation of extracellular signal‐regulated kinases (ERK). Although EGF can maintain hepatocyte functions up to day 5, no marked efffect was found with VIP. Conclusions VIP induces proliferation of human hepatocytes with little or no effect on hepatocyte differentiation. Further investigation of the role of VIP is required to determine if it may ultimately support therapeutic approaches of liver disease. |
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