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Sci Rep. 2015 Nov 19;5:16920. doi: 10.1038/srep16920.

Beneficial impact of Gpnmb and its significance as a biomarker in nonalcoholic steatohepatitis.

Author information

1
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama 700-8558, Japan.
2
Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama 700-8558, Japan.
3
Department of Diabetes and Metabolism, National Hospital Organization Okayama Medical center, Kita-ku, Okayama 701-1154, Japan.
4
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama 700-8558, Japan.
5
Animal Resource Development Unit, 2-2-3 Minatojima Minami, Chuou-ku, Kobe 650-0047, Japan.
6
Genetic Engineering Team, RIKEN Center for Life Science Technologies, 2-2-3 Minatojima Minami, Chuou-ku, Kobe 650-0047, Japan.

Abstract

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.

PMID:
26581806
PMCID:
PMC4652285
DOI:
10.1038/srep16920
[Indexed for MEDLINE]
Free PMC Article

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