Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, B‑3000 Leuven, Belgium.
Laboratory for Thrombosis Research, Department of Chemistry, University of Leuven Kulak Campus Kortrijk, B‑8500 Kortrijk, Belgium.
Mol Med Rep. 2017 Aug;16(2):1451-1458. doi: 10.3892/mmr.2017.6714. Epub 2017 Jun 7.
Previous studies, predominantly based on increased or decreased plasma levels, have reported conflicting data on a potential functional role of ADAMTS13 in the pathogenesis of liver diseases, including non‑alcoholic steatohepatitis (NASH). The aim of the current study was to evaluate whether ADAMTS13 deficiency affects development of NASH. Therefore, male wild‑type (WT) and Adamts13 deficient (Adamts13‑/‑) mice were kept on a steatosis‑inducing diet devoid of methionine and choline (MCD) or a control diet (MCC) for 4 weeks. Induction of NASH did not affect plasma ADAMTS13 antigen levels of WT mice. MCD as compared with MCC feeding resulted in reduced body and liver weight with no differences between the genotypes. Plasma levels of the liver enzymes AST and ALT were significantly higher for MCD vs. MCC fed Adamts13‑/‑ and WT mice, however were not different between the genotypes. Liver triglyceride levels were also higher after MCD feeding, but were not different between WT and Adamts13‑/‑ mice. Adamts13‑/‑ mice on the two diets exhibited higher insulin sensitivity when compared with WT mice. On the MCC diet, the genotype did not show clear histological abnormalities in the liver, whereas severe steatosis and fibrosis were observed on MCD diet, however were comparable for both genotypes. This was supported by comparably enhanced hepatic expression in the two genotypes on MCD diet of the steatosis marker CD36 and of the fibrosis marker tissue inhibitor of metalloproteinase 1. Thus, the results of the current study do not support a functional role of ADAMTS13 in this murine model of NASH.
先前的研究主要基于血浆水平的升高或降低，报告了关于 ADAMTS13 在包括非酒精性脂肪性肝炎（NASH）在内的肝脏疾病发病机制中的潜在功能作用的相互矛盾的数据。本研究的目的是评估 ADAMTS13 缺乏是否会影响 NASH 的发展。因此，雄性野生型（WT）和 Adamts13 缺陷型（Adamts13-/-）小鼠分别在缺乏蛋氨酸和胆碱的致脂肪变性饮食（MCD）或对照饮食（MCC）上饲养 4 周。NASH 的诱导并未影响 WT 小鼠的血浆 ADAMTS13 抗原水平。与 MCC 喂养相比，MCD 喂养导致体重和肝重减轻，但基因型之间无差异。与 MCC 喂养的 Adamts13-/-和 WT 小鼠相比，MCD 喂养的血浆肝酶 AST 和 ALT 水平显著升高，但基因型之间无差异。肝甘油三酯水平在 MCD 喂养后也升高，但 WT 和 Adamts13-/-小鼠之间无差异。与 WT 小鼠相比，MCD 喂养的 Adamts13-/-小鼠胰岛素敏感性更高。在 MCC 饮食中，两种基因型在肝脏中均未显示出明显的组织学异常，但在 MCD 饮食中观察到严重的脂肪变性和纤维化，且两种基因型之间无差异。这两种基因型在 MCD 饮食中脂肪变性标志物 CD36 和纤维化标志物组织金属蛋白酶抑制剂 1 的肝表达均增强，支持了这一结果。因此，本研究的结果不支持 ADAMTS13 在这种 NASH 小鼠模型中具有功能作用。
