Human hepatic progenitor cells express vasoactive intestinal peptide receptor type 2 and receive nerve endings.
BACKGROUND
We recently showed that human hepatic progenitor cells (HPCs) express muscarinic acetylcholine (Ach) receptor subtype 3 and that--following liver transplantation--HPC numbers are significantly reduced. To further elaborate on this, we examined whether HPC also express receptors for vasoactive intestinal peptide (VIP), which, besides Ach, also is an important parasympathetic neurotransmitter. VIP expressing nerves are known to be present in the liver.


METHODS
We performed immunohistochemistry for VIP receptor subtypes 1 and 2 (VIPR1 and 2), on sections of normal and diseased human liver (n=17), and double staining for VIPR2 and known HPC markers. We performed RT-PCR for VIPR1 and 2 on total RNA from purified rat HPC. To document the probability of direct interaction, we also performed double immunostaining for nerve markers and HPC markers on human liver sections.


RESULTS
VIPR2 immunostaining was clearly positive in HPC and reactive bile ductules on paraffin-embedded and frozen tissue sections. We could not demonstrate VIPR1 protein expression in the liver, with either of two VIPR1 antibodies tested. The presence of VIPR2 mRNA in HPC was confirmed by RT-PCR. Nerve endings were shown to abut on reactive bile ductules.


CONCLUSIONS
We show here for the first time that HPC express VIPR2 and receive nerve endings. These features, and the fact that HPC numbers are influenced by the presence or absence of the autonomic innervation of the liver, suggest a direct interaction.
Cassiman
David
D
Department of Hepatology, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium. David.cassiman@med.kuleuven.be
Sinelli
Nicoletta
N
Bockx
Ilse
I
Vander Borght
Sara
S
Petersen
Bryon
B
De Vos
Rita
R
van Pelt
Jos
J
Nevens
Frederik
F
Libbrecht
Louis
L
Roskams
Tania
T
D000818:Animals; D001341:Autonomic Nervous System; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology* / Q000294:innervation*; D009411:Nerve Endings / Q000033:anatomy & histology*; D051381:Rats; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000378:metabolism*; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism*
D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I