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Pathological implications of cadherin zonation in mouse liver

Abstract:

Both acute and chronic liver diseases are associated with ample re-modeling of the liver parenchyma leading to functional impairment, which is thus obviously the cause or the consequence of the disruption of the epithelial integrity. It was, therefore, the aim of this study to investigate the distribution of the adherens junction components E- and N-cadherin, which are important determinants of tissue cohesion. E-cadherin was expressed in periportal but not in perivenous hepatocytes. In contrast, N-cadherin was more enriched towards the perivenous hepatocytes. In agreement, beta-catenin, which links both cadherins via alpha-catenin to the actin cytoskeleton, was expressed ubiquitously. This zonal expression of cadherins was preserved in acute liver injury after treatment with acetaminophen or partial hepatectomy, but disrupted in chronic liver damage like in non-alcoholic steatohepatitis (NASH) or alpha1-antitrypsin deficiency. Hepatocyte proliferation during acetaminophen-induced liver damage was predominant at the boundary between the damaged perivenous and the intact periportal parenchyma indicating a minor contribution of periportal hepatocytes to liver regeneration. In NASH livers, an oval cell reaction was observed pointing to massive tissue damage coinciding with the gross impairment of hepatocyte proliferation. In the liver parenchyma, metabolic functions are distributed heterogeneously. For example, the expression of phosphoenolpyruvate carboxykinase and E-cadherin overlapped in periportal hepatocytes. Thus, during liver regeneration after acute damage, the intact periportal parenchyma might sustain essential metabolic support like glucose supply or ammonia detoxification. However, disruption of epithelial integrity during chronic challenges may increase susceptibility to metabolic liver diseases such as NASH or vice versa. This might suggest the regulatory integration of tissue cohesion and metabolic functions in the liver.

25687506

Projects: C6: Organization and function of the sinusoidal system and the liver lob...

Cell Mol Life Sci
Cell Mol Life Sci. 2015 Jul;72(13):2599-612. doi: 10.1007/s00018-015-1861-y. Epub 2015 Feb 17.
17th Feb 2015

M. Hempel, A. Schmitz, S. Winkler, O. Kucukoglu, S. Bruckner, C. Niessen, B. Christ

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[Sandra Brückner] [Bruno Christ]

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Liver lobule
Views: 1225
  • Created: 11th Nov 2015 at 11:12

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