Haberl Elisabeth M, Pohl Rebekka, Rein-Fischboeck Lisa, Feder Susanne, Sinal Christopher J, Buechler Christa
Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
Department of Pharmacology, Dalhousie University, Halifax, Canada.
Anticancer Res. 2018 May;38(5):2649-2657. doi: 10.21873/anticanres.12507.
BACKGROUND/AIM: Non-alcoholic steatohepatitis (NASH) is a risk factor for hepatocellular carcinoma (HCC). The adipokine chemerin protects from HCC and is reduced in human HCC. In this study, chemerin expression was analyzed in a murine model of NASH-HCC.
Serum and hepatic chemerin, and ex vivo chemerin receptor activation were monitored in NASH and NASH-HCC in mice fed a low-methionine diet deficient in choline after initiation of tumors by injection of diethylnitrosamine.
In non-tumorous liver tissues, the extent of hepatic steatosis, and the levels of proteins regulating hepatic lipids and liver fibrosis were similar in NASH and NASH-associated HCC. Systemic and hepatic chemerin, and chemerin receptor activation were not changed in HCC. Liver tumors only developed in diethylnitrosamine-injected mice and their number was increased in NASH. Chemerin protein was induced in liver in NASH, but was unchanged in HCC tissues.
Hepatic and serum chemerin and ex vivo analyzed chemerin receptor activation do not differ in murine NASH-associated HCC when compared to NASH. Hepatic tumors still develop despite high endogenous levels of serum and liver chemerin protein.
背景/目的：非酒精性脂肪性肝炎（NASH）是肝细胞癌（HCC）的一个危险因素。脂肪因子chemerin对HCC具有保护作用，且在人类HCC中表达降低。在本研究中，对NASH-HCC小鼠模型中的chemerin表达进行了分析。
通过注射二乙基亚硝胺诱发肿瘤后，对喂食低蛋氨酸胆碱缺乏饮食的小鼠的NASH和NASH-HCC模型监测血清和肝脏中的chemerin以及体外chemerin受体激活情况。
在非肿瘤性肝组织中，NASH和NASH相关HCC的肝脂肪变性程度以及调节肝脂质和肝纤维化的蛋白质水平相似。HCC中全身和肝脏的chemerin以及chemerin受体激活情况未发生改变。肝肿瘤仅在注射二乙基亚硝胺的小鼠中发生，且在NASH中其数量增加。NASH时肝脏中chemerin蛋白被诱导，但在HCC组织中未发生变化。
与NASH相比，在小鼠NASH相关HCC中，肝脏和血清中的chemerin以及体外分析的chemerin受体激活情况并无差异。尽管血清和肝脏中chemerin蛋白内源性水平较高，但肝肿瘤仍会发生。
