Khedr, MEMS; Abdelmotelb, AM; Bedwell, TA; Shtaya, A; Alzoubi, MN; Abu Hilal, M; Khakoo, SI
(2018)
Vasoactive intestinal peptide induces proliferation of human hepatocytes.
Cell Prolif, 51 (5).
e12482.
ISSN 1365-2184
https://doi.org/10.1111/cpr.12482
SGUL Authors: Shtaya, Anan BY
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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.
Item Type: |
Article
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Additional Information: |
This is the peer reviewed version of the following article: Khedr, MEMS, Abdelmotelb, AM, Bedwell, TA, et al. Vasoactive intestinal peptide induces proliferation of human hepatocytes. Cell Prolif. 2018; 51:e12482, which has been published in final form at https://doi.org/10.1111/cpr.12482. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. |
Keywords: |
Adult, Aged, Aged, 80 and over, Cell Differentiation, Cell Proliferation, Cell Survival, Cells, Cultured, DNA Replication, Epidermal Growth Factor, Female, Hepatocytes, Humans, Ki-67 Antigen, Liver, Male, Middle Aged, Mitogen-Activated Protein Kinases, Phosphorylation, RNA, Messenger, Vasoactive Intestinal Peptide, Liver, Cells, Cultured, Hepatocytes, Humans, Epidermal Growth Factor, Vasoactive Intestinal Peptide, Mitogen-Activated Protein Kinases, Ki-67 Antigen, RNA, Messenger, Cell Differentiation, Cell Proliferation, Cell Survival, DNA Replication, Phosphorylation, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, 0601 Biochemistry And Cell Biology, Oncology & Carcinogenesis |
SGUL Research Institute / Research Centre: |
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) |
Journal or Publication Title: |
Cell Prolif |
ISSN: |
1365-2184 |
Language: |
eng |
Dates: |
Date | Event |
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26 September 2018 | Published | 20 July 2018 | Published Online | 4 May 2018 | Accepted |
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Publisher License: |
Publisher's own licence |
Projects: |
Project ID | Funder | Funder ID |
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UNSPECIFIED | Liver and Pancreatic Research & Development Cancer Charity, Southampton, UK | UNSPECIFIED | UNSPECIFIED | University of Southampton, UK | UNSPECIFIED |
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PubMed ID: |
30028555 |
Web of Science ID: |
WOS:000445601400020 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/110028 |
Publisher's version: |
https://doi.org/10.1111/cpr.12482 |
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