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

• Published in: Scientific reports Vol. 5; no. 1; p. 16920
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19-11-2015; Nature Publishing Group
• Subjects: 13; 3T3-L1 Cells; 64/110; 692/163/2743/2037; 692/4017; 82; 82/58; Adipocytes - metabolism; Adipocytes - pathology; Adipose tissue; Adipose Tissue, White - metabolism; Animals; Biomarkers - metabolism; Calnexin; Calnexin - metabolism; Eye Proteins - blood; Eye Proteins - genetics; Eye Proteins - metabolism; Fatty liver; Female; Fibrosis; Gene Expression Regulation; Hepatic Stellate Cells - metabolism; Humanities and Social Sciences; Kupffer cells; Liver - metabolism; Liver - pathology; Liver Cirrhosis - complications; Liver Cirrhosis - pathology; Liver diseases; Logistic Models; Macrophages; Macrophages - metabolism; Male; Membrane Glycoproteins - blood; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Membrane proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; mRNA; multidisciplinary; Multivariate Analysis; Non-alcoholic Fatty Liver Disease - metabolism; Obesity; Obesity - complications; Obesity - pathology; Oxidative stress; Protein Binding; Rats, Inbred OLETF; Risk Factors; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Science; Steatosis; Stellate cells; Transgenic mice
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep16920

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.