Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease

被引：218

作者：

Niu, Lili ^{[1
,2
]}

Geyer, Philipp E. ^{[1
,2
]}

Albrechtsen, Nicolai J. Wewer ^{[1
,2
,3
,4
,5
]}

Gluud, Lise L. ^{[6
,7
]}

Santos, Alberto ^{[1
]}

Doll, Sophia ^{[1
,2
]}

Treit, Peter, V ^{[2
]}

Holst, Jens J. ^{[3
,4
]}

Knop, Filip K. ^{[4
,6
,8
]}

Vilsbol, Tina ^{[6
,8
]}

Junker, Anders ^{[6
,8
]}

Sachs, Stephan ^{[9
,10
]}

Stemmer, Kerstin ^{[9
,10
]}

Mueller, Timo D. ^{[9
,10
]}

Tschoep, Matthias H. ^{[9
,10
]}

Hofmann, Susanna M. ^{[11
,12
,13
]}

Mann, Matthias ^{[1
,2
]}

机构：

[1] Univ Copenhagen, Novo Nordisk Fdn Ctr Prot Res, Fac Hlth Sci, Copenhagen, Denmark

[2] Max Planck Inst Biochem, Dept Prote & Signal Transduct, Martinsried, Germany

[3] Univ Copenhagen, Fac Hlth & Med Sci, Dept Biomed Sci, Copenhagen, Denmark

[4] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Fac Hlth & Med Sci, Copenhagen, Denmark

[5] Univ Copenhagen, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark

[6] Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark

[7] Univ Copenhagen, Hvidovre Hosp, Med Div, Gastrounit, Hvidovre, Denmark

[8] Gentofte Univ Hosp, Steno Diabet Ctr Copenhagen, Clin Metab Physiol, Hellerup, Denmark

[9] Tech Univ Munich, Helmholtz Diabet Ctr, Helmholtz Ctr, Munich, Germany

[10] Tech Univ Munich, Div Metab Dis, Inst Diabet & Obes, Munich, Germany

[11] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Helmholtz Diabet Ctr, Inst Diabet & Regenerat, Neuherberg, Germany

[12] German Ctr Diabet Res DZD, Neuherberg, Germany

[13] Klinikum LMU, Med Klin & Poliklin 4, Munich, Germany

来源：

MOLECULAR SYSTEMS BIOLOGY | 2019年 / 15卷 / 03期

基金：

欧盟地平线“2020”;

关键词：

biomarker discovery; mass spectrometry; NAFLD; NASH; plasma proteome profiling; DIPEPTIDYL PEPTIDASE-4; BIOMARKER DISCOVERY; INSULIN-RESISTANCE; FIBROSIS; STEATOHEPATITIS; GALECTIN-3; NASH; SITAGLIPTIN; CIRRHOSIS; OBESITY;

D O I：

10.15252/msb.20188793

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 (PICR) 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.

引用

页数：16

共 79 条

[51] Plasma Concentrations of Afamin Are Associated With Prevalent and Incident Type 2 Diabetes: A Pooled Analysis in More Than 20,000 Individuals [J].