TRPC6-protein expression in the elderly and in liver disease

Abstract

The transient receptor potential canonical 6 (TRPC6) channel has been studied in pathologies of the hepatobiliary system. Information on the localization of TRPC6-protein in anatomical and histological structures of the human hepatobiliary system in elderly with and without liver disease is lacking. Samples were obtained from twelve nitrite pickling salt-ethanol-polyethylene glycol-fixed corpses of the four anatomical liver lobes, collum and the remaining gallbladder, the common bile duct (gender: 5 females, 41.67%; age [years]: median 84, range 20; postmortem interval before fixation [h]: median 60, range 74.15). Orienting histomorphologic assessment was done in a hematoxylin-eosin stain. Immunohistochemical labelling of TRPC6 was carried out following a cross-evaluation scheme. TRPC6-immunoreactivity was assessed regarding intensity (semi-quantification, three independent observers) and area (optical threshold method). Explorative statistical analyses were performed using R (inter-rater-reliability: Fleiss' kappa; comparisons: Wilcoxon-Rank-sum-test). Extensive autolysis was found in the liver of one and the biliary samples of three corpses. Extensive liver disease was found in 4 corpses, while 8 corpses only showed age-appropriate degeneration. Only the intrahepatic connective tissue showed no TRPC6-immunoreactivity. Individuals with extensively diseased livers exhibited statistically significantly less TRPC6-immunoreactive area in the bile duct and liver tissue while statistically significant more TRPC6-immunoreactive area in the gallbladder compared to individuals with age-appropriate degeneration of the liver only in the respective organ. Age-associated degeneration of the hepatobiliary system is likely to be associated with widespread, homogenous TRPC6-expression. Liver disease potentially influences the distribution of TRPC6-protein within the liver and within the biliary tract in elderly.