Beneficial impact of Gpnmb and its significance as a biomarker in nonalcoholic steatohepatitis.
Beneficial impact of Gpnmb and its significance as a biomarker in nonalcoholic steatohepatitis.
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DOI：
10.1038/srep16920
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发表时间：
2015-11-19
影响因子：
4.6
通讯作者：
Wada J
中科院分区：
文献类型：
--
作者：
Katayama A;Nakatsuka A;Eguchi J;Murakami K;Teshigawara S;Kanzaki M;Nunoue T;Hida K;Wada N;Yasunaka T;Ikeda F;Takaki A;Yamamoto K;Kiyonari H;Makino H;Wada J
非酒精性脂肪性肝病（NAFLD）是世界范围内最常见的慢性肝病。Gpnmb被归类为1型膜蛋白，其可溶性形式通过adam10介导的裂解分泌。Gpnmb mRNA在Kupffer细胞和白色脂肪组织（WATs）中被发现，最近在肥胖中被发现上调。在这里，我们培育了aP2启动子驱动的Gpnmb转基因（Tg）小鼠，在饮食诱导的肥胖模型中，Gpnmb的过表达改善了肝脏的脂肪积累和纤维化。Gpnmb Tg小鼠血清中Gpnmb的可溶性形式升高，Gpnmb在肝巨噬细胞和星状细胞中富集，与钙连联素相互作用，导致氧化应激降低。非酒精性脂肪性肝炎患者血清可溶性GPNMB浓度高于单纯性脂肪变性患者。GPNMB是肥胖症NAFLD发生和发展的一个有前景的生物标志物和治疗靶点。
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Gpnmb is classified as a type 1 membrane protein and its soluble form is secreted by ADAM10-mediated cleavage. Gpnmb mRNA was found in the Kupffer cells and white adipose tissues (WATs) and its upregulation in obesity was recently found. Here, we generated aP2 promoter-driven Gpnmb transgenic (Tg) mice and the overexpression of Gpnmb ameliorated the fat accumulation and fibrosis of the liver in diet-induced obesity model. Soluble form of Gpnmb in sera was elevated in Gpnmb Tg mice and Gpnmb concentrated in hepatic macrophages and stellate cells interacted with calnexin, which resulted in the reduction of oxidative stress. In the patients with non-alcoholic steatohepatitis, serum soluble GPNMB concentrations were higher compared with the patients with simple steatosis. The GPNMB is a promising biomarker and therapeutic target for the development and progression of NAFLD in obesity.