Introduction There has been increasing interest in the possibility of using spontaneous canine hepatic disease as a model for those in human beings.1 Dogs with congenital portosystemic shunts (CPSS) have hypoplasia of the liver and intrahepatic portal veins. While the condition is extremely rare in people, it is more common in dogs. Surgical CPSS attenuation results in liver growth and development of the intrahepatic portal vasculature, associated with clinical improvement.2 The precise mechanism of this hepatic response is unknown; we hypothesised that it is due to hepatic regeneration and angiogenesis. The study aimed to measure the mRNA expression of growth factors and receptors involved in liver regeneration and angiogenesis in liver biopsies from dogs with CPSS before and after partial attenuation.
Methods Dogs treated for CPSS were prospectively recruited to the study and liver biopsy samples were collected and placed in RNAlater. The expression of nine genes related to liver regeneration and angiogenesis were evaluated using quantitative polymerase chain reaction (qPCR). Differences in gene expression were assessed using independent or paired T tests. Significance was set at the 5% level (p=0.05).
Results Liver biopsies were collected from 49 CPSS dogs to seven control dogs. 24 dogs tolerated complete attenuation of their CPSS and 25 tolerated partial attenuation. A second surgery was performed in all partial attenuation dogs to achieve complete attenuation and a follow-up biopsy was taken. HGF mRNA expression was significantly decreased in CPSS dogs compared with controls. There were significant increases in mRNA expression of HGF, MAT2α andVEGFR2 following partial CPSS attenuation. In addition, dogs that could tolerate complete attenuation had significantly greater MAT2α, VEGFR2 and TGFβR2 mRNA expression.
Conclusion The results of this study indicate that the liver regeneration and angiogenesis are involved in the hepatic response to surgery in dogs with CPSS. This suggests that canine CPSS could be a useful, naturally occurring model of liver regeneration.
Competing interests None declared.
References 1. Kruitwagen HS, Arends B, Spee B, et al. Recombinant hepatocyte growth factor treatment in a canine model of congenital liver hypoplasia. Liver Int 2011;31:940–9.
2. Lee KC, Lipscomb VJ, Lamb CR, et al. Association of portovenographic findings with outcome in dogs receiving surgical treatment for single congenital portosystemic shunts: 45 cases (2000-2004). J Am Vet Med Assoc 2006;229:1122–9.
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