Annexin A6 protein is downregulated in human hepatocellular carcinoma

被引:23
作者
Meier, Elisabeth M. [1 ]
Rein-Fischboeck, Lisa [1 ]
Pohl, Rebekka [1 ]
Wanninger, Josef [1 ]
Hoy, Andrew J. [2 ,3 ]
Grewal, Thomas [4 ]
Eisinger, Kristina [1 ]
Krautbauer, Sabrina [1 ]
Liebisch, Gerhard [5 ]
Weiss, Thomas S. [6 ]
Buechler, Christa [1 ]
机构
[1] Regensburg Univ Hosp, Dept Internal Med 1, D-93042 Regensburg, Germany
[2] Univ Sydney, Dept Physiol, Sch Med Sci, Sydney, NSW 2006, Australia
[3] Univ Sydney, Bosch Inst, Sydney Med Sch,Charles Perkins Ctr, Boden Inst Obes Nutr Exercise & Eating Disorders, Sydney, NSW 2006, Australia
[4] Univ Sydney, Fac Pharm, Sydney, NSW 2006, Australia
[5] Regensburg Univ Hosp, Inst Clin Chem & Lab Med, Regensburg, Germany
[6] Univ Children Hosp KUNO, Regensburg Univ Hosp, Regensburg, Germany
关键词
Nonalcoholic fatty liver disease; Hepatocyte; Hepatic stellate cells; Cirrhosis; FATTY LIVER-DISEASE; HIGH-THROUGHPUT QUANTIFICATION; INDUCED OBESE MICE; NONALCOHOLIC STEATOHEPATITIS; CHOLESTEROL TRANSPORT; MASS-SPECTROMETRY; INTRACELLULAR-DISTRIBUTION; LIPIDOMIC ANALYSIS; ADIPONECTIN; CELLS;
D O I
10.1007/s11010-016-2735-9
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Annexin A6 (AnxA6) is a lipid-binding protein highly expressed in the liver, regulating cholesterol homeostasis and signaling pathways with a role in liver physiology. Here, we analyzed whether hepatic AnxA6 levels are affected by pathological conditions that are associated with liver dysfunction and liver injury. AnxA6 levels in the fatty liver of mice fed a high-fat diet, in ob/ob and db/db animals and in human fatty liver are comparable to controls. Similarly, AnxA6 levels appear unaffected in murine nonalcoholic steatohepatitis and human liver fibrosis. Accordingly, adiponectin, lysophosphatidylcholine, palmitate, and TGFbeta, all of which have a role in liver injury, do not affect AnxA6 expression in human hepatocytes. Likewise, adiponectin and IL8 do not alter AnxA6 levels in primary human hepatic stellate cells. However, in hepatic tumors of 18 patients, AnxA6 protein levels are substantially reduced compared to nontumorous tissues. AnxA6 mRNA is even increased in the tumors suggesting that posttranscriptional mechanisms are involved herein. Lipidomic analysis shows trends toward elevated cholesteryl ester and sphingomyelin in the tumor samples, yet the ratio of tumor to nontumorous AnxA6 does not correlate with these lipids. The current study shows that AnxA6 is specifically reduced in human hepatocellular carcinoma suggesting a role of this protein in hepatocarcinogenesis.
引用
收藏
页码:81 / 90
页数:10
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