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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism
  • Adipocytes / pathology
  • Adipose Tissue, White / metabolism
  • Animals
  • Biomarkers / metabolism
  • Calnexin / metabolism
  • Eye Proteins / blood
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • Female
  • Gene Expression Regulation
  • Hepatic Stellate Cells / metabolism
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / pathology
  • Logistic Models
  • Macrophages / metabolism
  • Male
  • Membrane Glycoproteins / blood
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Multivariate Analysis
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Obesity / complications
  • Obesity / pathology
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Inbred OLETF
  • Risk Factors

Substances

  • Biomarkers
  • Eye Proteins
  • GPNMB protein, human
  • Gpnmb protein, mouse
  • Gpnmb protein, rat
  • Membrane Glycoproteins
  • RNA, Messenger
  • Calnexin