Correction: Aberrant Gene Expression in Dogs with Portosystemic Shunts

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.

Clinical Characteristics, Serum Biochemical Changes, and Expression Profile of Serum Cfa-miRNAs in Dogs Confirmed to Have Congenital Portosystemic Shunts Accompanied by Liver Pathologies

“…Clinical characteristics of dogs included in our study are largely consistent with the data reported in previous literature [28]. Indeed, we noticed that congenital EHPSS is mostly diagnosed in small pedigree dogs, which may be reasoned to the aberrant lower hepatic expression of vascular cell adhesion molecule gene (VCAM1) that plays a potential role in the development of intrahepatic portal vascularization, whereas IHPSS was mostly observed among large breeds, which may be related to the hepatic over-expression of WEE1 gene that results in suppressing the post-natal closure of ductus venosus [29]. In this instance, Yorkshire terriers were the most predominant among breeds that are confirmed to have various morphologies of EHPSS except the splenophreic shunt, which is more frequently diagnosed in black Russian toy terrier and frequently observed in some cases in Moscow but not published in other studies up to the present time.…”