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

Akihiro Katayama, Atsuko Nakatsuka, Jun Eguchi, Kazutoshi Murakami, Sanae Teshigawara, Motoko Kanzaki, Tomokazu Nunoue, Kazuyuki Hida, Nozomu Wada, Tetsuya Yasunaka, Fusao Ikeda, Akinobu Takaki, Kazuhide Yamamoto, Hiroshi Kiyonari, Hirofumi Makino, Jun Wada

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number16920
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - Nov 19 2015

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Obesity
Biomarkers
Transgenic Mice
Calnexin
Hepatic Stellate Cells
White Adipose Tissue
Kupffer Cells
Fatty Liver
Serum
Liver Cirrhosis
Liver Diseases
Membrane Proteins
Oxidative Stress
Chronic Disease
Up-Regulation
Fats
Macrophages
Diet
Messenger RNA
Non-alcoholic Fatty Liver Disease

ASJC Scopus subject areas

  • General

Cite this

Beneficial impact of Gpnmb and its significance as a biomarker in nonalcoholic steatohepatitis. / Katayama, Akihiro; Nakatsuka, Atsuko; Eguchi, Jun; Murakami, Kazutoshi; Teshigawara, Sanae; Kanzaki, Motoko; Nunoue, Tomokazu; Hida, Kazuyuki; Wada, Nozomu; Yasunaka, Tetsuya; Ikeda, Fusao; Takaki, Akinobu; Yamamoto, Kazuhide; Kiyonari, Hiroshi; Makino, Hirofumi; Wada, Jun.

In: Scientific Reports, Vol. 5, 16920, 19.11.2015.

Research output: Contribution to journalArticle

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AU - Teshigawara, Sanae

AU - Kanzaki, Motoko

AU - Nunoue, Tomokazu

AU - Hida, Kazuyuki

AU - Wada, Nozomu

AU - Yasunaka, Tetsuya

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AU - Takaki, Akinobu

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AU - Kiyonari, Hiroshi

AU - Makino, Hirofumi

AU - Wada, Jun

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