Aberrant gene expression in dogs with portosystemic shunts

F.G. van Steenbeek; L. van den Bossche; G.C.M. Grinwis; A. Kummeling; I.H. Gils; M.G. Koerkamp; D. van Leenen; F.C. Holstege; L.C. Penning; J. Rothuizen; P.A.J. Leegwater; B. Spee

doi:10.1371/journal.pone.0057662

Aberrant gene expression in dogs with portosystemic shunts

F.G. van Steenbeek, L. van den Bossche, G.C.M. Grinwis, A. Kummeling, I.H. Gils, M.G. Koerkamp, D. van Leenen, F.C. Holstege, L.C. Penning, J. Rothuizen, P.A.J. Leegwater, B. Spee

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Abstract Congenital portosystemic shunts are developmental anomalies of the splanchnic vascular system that cause portal blood to bypass the liver. Large-breed dogs are predisposed for intrahepatic portosystemic shunts (IHPSS) and small-breed dogs for extrahepatic portosystemic shunts (EHPSS). While the phenotype resulting from portal bypass of the liver of the two types of shunt is identical, the genotype and molecular pathways involved are probably different. The aim of this study was to gain insight into the pathways involved in the different types of portosystemic shunting. Microarray analysis of mRNA expression in liver tissue from dogs with EHPSS and IHPSS revealed that the expression of 26 genes was altered in either IHPSS or EHPSS samples compared with that in liver samples from control dogs. Quantitative real-time PCR of these genes in 14 IHPSS, 17 EHPSS, and 8 control liver samples revealed a significant differential expression of ACBP, CCBL1, GPC3, HAMP, PALLD, VCAM1, and WEE1. Immunohistochemistry and Western blotting confirmed an increased expression of VCAM1 in IHPSS but its absence in EHPSS, an increased WEE1 expression in IHPSS but not in EHPSS, and a decreased expression of CCBL1 in both shunt types. Regarding their physiologic functions, these findings may indicate a causative role for VCAM1 in IHPSS and WEE1 for IHPSS. CCBL1 could be an interesting candidate to study not yet elucidated aspects in the pathophysiology of hepatic encephalopathy. PMID:23451256[PubMed - in process] PMCID:PMC3581512

Original language	Undefined/Unknown
Pages (from-to)	e57662
Number of pages	1
Journal	PLoS One
Volume	8
Issue number	2
DOIs	https://doi.org/10.1371/journal.pone.0057662
Publication status	Published - 2013

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10.1371/journal.pone.0057662

Aberrant gene expression in dogs with portosystemic shunts
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http://www.ncbi.nlm.nih.gov/pubmed/23451256

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@article{b996c1d59b2c4b3c812ec9cd1e942edd,

title = "Aberrant gene expression in dogs with portosystemic shunts",

abstract = "Abstract Congenital portosystemic shunts are developmental anomalies of the splanchnic vascular system that cause portal blood to bypass the liver. Large-breed dogs are predisposed for intrahepatic portosystemic shunts (IHPSS) and small-breed dogs for extrahepatic portosystemic shunts (EHPSS). While the phenotype resulting from portal bypass of the liver of the two types of shunt is identical, the genotype and molecular pathways involved are probably different. The aim of this study was to gain insight into the pathways involved in the different types of portosystemic shunting. Microarray analysis of mRNA expression in liver tissue from dogs with EHPSS and IHPSS revealed that the expression of 26 genes was altered in either IHPSS or EHPSS samples compared with that in liver samples from control dogs. Quantitative real-time PCR of these genes in 14 IHPSS, 17 EHPSS, and 8 control liver samples revealed a significant differential expression of ACBP, CCBL1, GPC3, HAMP, PALLD, VCAM1, and WEE1. Immunohistochemistry and Western blotting confirmed an increased expression of VCAM1 in IHPSS but its absence in EHPSS, an increased WEE1 expression in IHPSS but not in EHPSS, and a decreased expression of CCBL1 in both shunt types. Regarding their physiologic functions, these findings may indicate a causative role for VCAM1 in IHPSS and WEE1 for IHPSS. CCBL1 could be an interesting candidate to study not yet elucidated aspects in the pathophysiology of hepatic encephalopathy. PMID:23451256[PubMed - in process] PMCID:PMC3581512",

author = "{van Steenbeek}, F.G. and {van den Bossche}, L. and G.C.M. Grinwis and A. Kummeling and I.H. Gils and M.G. Koerkamp and {van Leenen}, D. and F.C. Holstege and L.C. Penning and J. Rothuizen and P.A.J. Leegwater and B. Spee",

year = "2013",

doi = "10.1371/journal.pone.0057662",

language = "Undefined/Unknown",

volume = "8",

pages = "e57662",

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T1 - Aberrant gene expression in dogs with portosystemic shunts

AU - van Steenbeek, F.G.

AU - van den Bossche, L.

AU - Grinwis, G.C.M.

AU - Kummeling, A.

AU - Gils, I.H.

AU - Koerkamp, M.G.

AU - van Leenen, D.

AU - Holstege, F.C.

AU - Penning, L.C.

AU - Rothuizen, J.

AU - Leegwater, P.A.J.

AU - Spee, B.

PY - 2013

Y1 - 2013

N2 - Abstract Congenital portosystemic shunts are developmental anomalies of the splanchnic vascular system that cause portal blood to bypass the liver. Large-breed dogs are predisposed for intrahepatic portosystemic shunts (IHPSS) and small-breed dogs for extrahepatic portosystemic shunts (EHPSS). While the phenotype resulting from portal bypass of the liver of the two types of shunt is identical, the genotype and molecular pathways involved are probably different. The aim of this study was to gain insight into the pathways involved in the different types of portosystemic shunting. Microarray analysis of mRNA expression in liver tissue from dogs with EHPSS and IHPSS revealed that the expression of 26 genes was altered in either IHPSS or EHPSS samples compared with that in liver samples from control dogs. Quantitative real-time PCR of these genes in 14 IHPSS, 17 EHPSS, and 8 control liver samples revealed a significant differential expression of ACBP, CCBL1, GPC3, HAMP, PALLD, VCAM1, and WEE1. Immunohistochemistry and Western blotting confirmed an increased expression of VCAM1 in IHPSS but its absence in EHPSS, an increased WEE1 expression in IHPSS but not in EHPSS, and a decreased expression of CCBL1 in both shunt types. Regarding their physiologic functions, these findings may indicate a causative role for VCAM1 in IHPSS and WEE1 for IHPSS. CCBL1 could be an interesting candidate to study not yet elucidated aspects in the pathophysiology of hepatic encephalopathy. PMID:23451256[PubMed - in process] PMCID:PMC3581512

AB - Abstract Congenital portosystemic shunts are developmental anomalies of the splanchnic vascular system that cause portal blood to bypass the liver. Large-breed dogs are predisposed for intrahepatic portosystemic shunts (IHPSS) and small-breed dogs for extrahepatic portosystemic shunts (EHPSS). While the phenotype resulting from portal bypass of the liver of the two types of shunt is identical, the genotype and molecular pathways involved are probably different. The aim of this study was to gain insight into the pathways involved in the different types of portosystemic shunting. Microarray analysis of mRNA expression in liver tissue from dogs with EHPSS and IHPSS revealed that the expression of 26 genes was altered in either IHPSS or EHPSS samples compared with that in liver samples from control dogs. Quantitative real-time PCR of these genes in 14 IHPSS, 17 EHPSS, and 8 control liver samples revealed a significant differential expression of ACBP, CCBL1, GPC3, HAMP, PALLD, VCAM1, and WEE1. Immunohistochemistry and Western blotting confirmed an increased expression of VCAM1 in IHPSS but its absence in EHPSS, an increased WEE1 expression in IHPSS but not in EHPSS, and a decreased expression of CCBL1 in both shunt types. Regarding their physiologic functions, these findings may indicate a causative role for VCAM1 in IHPSS and WEE1 for IHPSS. CCBL1 could be an interesting candidate to study not yet elucidated aspects in the pathophysiology of hepatic encephalopathy. PMID:23451256[PubMed - in process] PMCID:PMC3581512

U2 - 10.1371/journal.pone.0057662

DO - 10.1371/journal.pone.0057662

M3 - Article

SN - 1932-6203

VL - 8

SP - e57662

JO - PLoS One

JF - PLoS One

IS - 2

ER -