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Hepatocyte GP73 expression in Wilson disease.
J Hepatol. 2009 Sep; 51(3):557-64.JH

Abstract

BACKGROUND/AIMS

Wilson disease (WD) is a disorder of copper transport caused by mutations within the ATP7B gene. WD is phenotypically variable and can present with predominantly hepatic or neurologic manifestations. The mechanisms responsible for this variability are unknown. GP73, a Golgi membrane protein, is expressed in hepatocytes in response to acute and chronic liver disease.

METHODS

Hepatocyte GP73 expression was examined in the livers of WD patients by semiquantitative immunohistochemistry. GP73 mRNA levels were measured in mice with a deletion of the WD gene (Atp7b(-/-)) by real-time PCR, and these values were compared to the concomitant histological abnormalities and previously reported copper levels.

RESULTS

Hepatocyte GP73 expression was more frequently observed in patients with hepatic versus neurologic presentation (79% vs. 30%, p<0.05). Furthermore, GP73 expression was significantly higher (44.7+/-14.0 vs. 2.0+/-0.81, p<0.05) in patients with hepatic phenotype. In Atp7b(-/-) mice, GP73 mRNA was significantly elevated at 20-46 weeks of age, coincident with extensive hepatic inflammation and fibrosis, but not at 6 weeks, when hepatic histology was normal despite significant copper overload. GP73 mRNA levels normalized concomitantly with the resolution of hepatic injury at 60-weeks. However, in tumor-like nodules GP73 was strikingly elevated.

CONCLUSION

Increased hepatocyte GP73 expression is more commonly a feature of hepatic than neurologic WD, and is triggered in response to inflammation, fibrosis, and dysplasia, rather than copper overload.

Authors+Show Affiliations

Division of Gastroenterology, Hepatology and Nutrition, Loyola University Medical Center, Maywood, IL 60153, USA. LMWright@lumc.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19596473

Citation

Wright, Lorinda M., et al. "Hepatocyte GP73 Expression in Wilson Disease." Journal of Hepatology, vol. 51, no. 3, 2009, pp. 557-64.
Wright LM, Huster D, Lutsenko S, et al. Hepatocyte GP73 expression in Wilson disease. J Hepatol. 2009;51(3):557-64.
Wright, L. M., Huster, D., Lutsenko, S., Wrba, F., Ferenci, P., & Fimmel, C. J. (2009). Hepatocyte GP73 expression in Wilson disease. Journal of Hepatology, 51(3), 557-64. https://doi.org/10.1016/j.jhep.2009.05.029
Wright LM, et al. Hepatocyte GP73 Expression in Wilson Disease. J Hepatol. 2009;51(3):557-64. PubMed PMID: 19596473.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatocyte GP73 expression in Wilson disease. AU - Wright,Lorinda M, AU - Huster,Dominik, AU - Lutsenko,Svetlana, AU - Wrba,Fritz, AU - Ferenci,Peter, AU - Fimmel,Claus J, Y1 - 2009/06/25/ PY - 2009/01/05/received PY - 2009/04/29/revised PY - 2009/05/25/accepted PY - 2009/7/15/entrez PY - 2009/7/15/pubmed PY - 2010/1/28/medline SP - 557 EP - 64 JF - Journal of hepatology JO - J. Hepatol. VL - 51 IS - 3 N2 - BACKGROUND/AIMS: Wilson disease (WD) is a disorder of copper transport caused by mutations within the ATP7B gene. WD is phenotypically variable and can present with predominantly hepatic or neurologic manifestations. The mechanisms responsible for this variability are unknown. GP73, a Golgi membrane protein, is expressed in hepatocytes in response to acute and chronic liver disease. METHODS: Hepatocyte GP73 expression was examined in the livers of WD patients by semiquantitative immunohistochemistry. GP73 mRNA levels were measured in mice with a deletion of the WD gene (Atp7b(-/-)) by real-time PCR, and these values were compared to the concomitant histological abnormalities and previously reported copper levels. RESULTS: Hepatocyte GP73 expression was more frequently observed in patients with hepatic versus neurologic presentation (79% vs. 30%, p<0.05). Furthermore, GP73 expression was significantly higher (44.7+/-14.0 vs. 2.0+/-0.81, p<0.05) in patients with hepatic phenotype. In Atp7b(-/-) mice, GP73 mRNA was significantly elevated at 20-46 weeks of age, coincident with extensive hepatic inflammation and fibrosis, but not at 6 weeks, when hepatic histology was normal despite significant copper overload. GP73 mRNA levels normalized concomitantly with the resolution of hepatic injury at 60-weeks. However, in tumor-like nodules GP73 was strikingly elevated. CONCLUSION: Increased hepatocyte GP73 expression is more commonly a feature of hepatic than neurologic WD, and is triggered in response to inflammation, fibrosis, and dysplasia, rather than copper overload. SN - 1600-0641 UR - https://www.unboundmedicine.com/medline/citation/19596473/Hepatocyte_GP73_expression_in_Wilson_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-8278(09)00398-5 DB - PRIME DP - Unbound Medicine ER -