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Vasoactive intestinal peptide induces proliferation of human hepatocytes

Vasoactive intestinal peptide induces proliferation of human hepatocytes
Vasoactive intestinal peptide induces proliferation of human hepatocytes
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.
1365-2184
1-12
Khedr, M.E.M.S.
37c876ff-7226-4d51-bd20-dfe0bbca3d73
Abdelmotelb, A.M.
47ec298b-4ec1-48e4-8a19-39f2235de4a5
Bedwell, Tom A
2db91b75-c2a9-468a-8d30-864bf5ca01e3
Shtaya, A.
a8b99cef-13c3-4a43-a799-d6d13799ab2b
Alzoubi, M.N.
6842d18c-af9f-4a0b-875c-1e82bbc3c583
Abu Hilal, M.
384e1c60-8519-4eed-8e92-91775aad4c47
Khakoo, S.I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Khedr, M.E.M.S.
37c876ff-7226-4d51-bd20-dfe0bbca3d73
Abdelmotelb, A.M.
47ec298b-4ec1-48e4-8a19-39f2235de4a5
Bedwell, Tom A
2db91b75-c2a9-468a-8d30-864bf5ca01e3
Shtaya, A.
a8b99cef-13c3-4a43-a799-d6d13799ab2b
Alzoubi, M.N.
6842d18c-af9f-4a0b-875c-1e82bbc3c583
Abu Hilal, M.
384e1c60-8519-4eed-8e92-91775aad4c47
Khakoo, S.I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273

Khedr, M.E.M.S., Abdelmotelb, A.M., Bedwell, Tom A, Shtaya, A., Alzoubi, M.N., Abu Hilal, M. and Khakoo, S.I. (2018) Vasoactive intestinal peptide induces proliferation of human hepatocytes. Cell Proliferation, 51 (5), 1-12, [e12482]. (doi:10.1111/cpr.12482).

Record type: Article

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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VIP manuscript Khedr - Accepted Manuscript
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Khedr et al 2018 Cell Proliferation - Version of Record
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More information

Accepted/In Press date: 4 May 2018
e-pub ahead of print date: 20 July 2018
Published date: October 2018

Identifiers

Local EPrints ID: 422961
URI: http://eprints.soton.ac.uk/id/eprint/422961
ISSN: 1365-2184
PURE UUID: 9b1eec0f-a6a3-410e-abbf-01899c1dec3f
ORCID for M.E.M.S. Khedr: ORCID iD orcid.org/0000-0001-9942-4409

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Date deposited: 08 Aug 2018 16:30
Last modified: 17 Dec 2019 05:18

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Contributors

Author: M.E.M.S. Khedr ORCID iD
Author: A.M. Abdelmotelb
Author: Tom A Bedwell
Author: A. Shtaya
Author: M.N. Alzoubi
Author: M. Abu Hilal
Author: S.I. Khakoo

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