TY - JOUR
T1 - Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease
AU - Niu, Lili
AU - Geyer, Philipp E.
AU - Albrechtsen, Nicolai Jacob Wewer
AU - Gluud, Lise L
AU - Santos, Alberto
AU - Doll, Sophia
AU - Treit, Peter V
AU - Holst, Jens J
AU - Knop, Filip K
AU - Vilsbøll, Tina
AU - Junker, Anders
AU - Sachs, Stephan
AU - Stemmer, Kerstin
AU - Müller, Timo D
AU - Tschöp, Matthias H
AU - Hofmann, Susanna M
AU - Mann, Matthias
PY - 2019
Y1 - 2019
N2 - Non-alcoholic fatty liver disease (NAFLD) affects 25% of the population and can progress to cirrhosis with limited treatment options. As the liver secretes most of the blood plasma proteins, liver disease may affect the plasma proteome. Plasma proteome profiling of 48 patients with and without cirrhosis or NAFLD revealed six statistically significantly changing proteins (ALDOB, APOM, LGALS3BP, PIGR, VTN, and AFM), two of which are already linked to liver disease. Polymeric immunoglobulin receptor (PIGR) was significantly elevated in both cohorts by 170% in NAFLD and 298% in cirrhosis and was further validated in mouse models. Furthermore, a global correlation map of clinical and proteomic data strongly associated DPP4, ANPEP, TGFBI, PIGR, and APOE with NAFLD and cirrhosis. The prominent diabetic drug target DPP4 is an aminopeptidase like ANPEP, ENPEP, and LAP3, all of which are up-regulated in the human or mouse data. Furthermore, ANPEP and TGFBI have potential roles in extracellular matrix remodeling in fibrosis. Thus, plasma proteome profiling can identify potential biomarkers and drug targets in liver disease.
AB - Non-alcoholic fatty liver disease (NAFLD) affects 25% of the population and can progress to cirrhosis with limited treatment options. As the liver secretes most of the blood plasma proteins, liver disease may affect the plasma proteome. Plasma proteome profiling of 48 patients with and without cirrhosis or NAFLD revealed six statistically significantly changing proteins (ALDOB, APOM, LGALS3BP, PIGR, VTN, and AFM), two of which are already linked to liver disease. Polymeric immunoglobulin receptor (PIGR) was significantly elevated in both cohorts by 170% in NAFLD and 298% in cirrhosis and was further validated in mouse models. Furthermore, a global correlation map of clinical and proteomic data strongly associated DPP4, ANPEP, TGFBI, PIGR, and APOE with NAFLD and cirrhosis. The prominent diabetic drug target DPP4 is an aminopeptidase like ANPEP, ENPEP, and LAP3, all of which are up-regulated in the human or mouse data. Furthermore, ANPEP and TGFBI have potential roles in extracellular matrix remodeling in fibrosis. Thus, plasma proteome profiling can identify potential biomarkers and drug targets in liver disease.
U2 - 10.15252/msb.20188793
DO - 10.15252/msb.20188793
M3 - Journal article
C2 - 30824564
VL - 15
JO - Molecular Systems Biology
JF - Molecular Systems Biology
SN - 1744-4292
M1 - e8793
ER -