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

Lili Niu; Philipp E. Geyer; Nicolai Jacob Wewer Albrechtsen; Lise L Gluud; Alberto Santos; Sophia Doll; Peter V Treit; Jens J Holst; Filip K Knop; Tina Vilsbøll; Anders Junker; Stephan Sachs; Kerstin Stemmer; Timo D Müller; Matthias H Tschöp; Susanna M Hofmann; Matthias Mann

doi:10.15252/msb.20188793

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

Lili Niu, Philipp E. Geyer, Nicolai Jacob Wewer Albrechtsen, Lise L Gluud, Alberto Santos, Sophia Doll, Peter V Treit, Jens J Holst, Filip K Knop, Tina Vilsbøll, Anders Junker, Stephan Sachs, Kerstin Stemmer, Timo D Müller, Matthias H Tschöp, Susanna M Hofmann, Matthias Mann

55 Citations (Scopus)

35 Downloads (Pure)

Abstract

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.

Original language	English
Article number	e8793
Journal	Molecular Systems Biology
Volume	15
Number of pages	16
ISSN	1744-4292
DOIs	https://doi.org/10.15252/msb.20188793
Publication status	Published - Mar 2019

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.15252/msb.20188793Licence: CC BY

Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver diseaseFinal published version, 2.3 MBLicence: CC BY

Cite this

Niu, L., Geyer, P. E., Albrechtsen, N. J. W., Gluud, L. L., Santos, A., Doll, S., Treit, P. V., Holst, J. J., Knop, F. K., Vilsbøll, T., Junker, A., Sachs, S., Stemmer, K., Müller, T. D., Tschöp, M. H., Hofmann, S. M., & Mann, M. (2019). Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease. Molecular Systems Biology, 15, Article e8793. https://doi.org/10.15252/msb.20188793

Niu, L, Geyer, PE, Albrechtsen, NJW , Gluud, LL , Santos, A, Doll, S, Treit, PV, Holst, JJ , Knop, FK , Vilsbøll, T, Junker, A, Sachs, S, Stemmer, K, Müller, TD, Tschöp, MH, Hofmann, SM & Mann, M 2019, 'Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease', Molecular Systems Biology, vol. 15, e8793. https://doi.org/10.15252/msb.20188793

@article{45ad40e110014d1fb2a619704b9c070b,

title = "Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease",

abstract = "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.",

author = "Lili Niu and Geyer, {Philipp E.} and Albrechtsen, {Nicolai Jacob Wewer} and Gluud, {Lise L} and Alberto Santos and Sophia Doll and Treit, {Peter V} and Holst, {Jens J} and Knop, {Filip K} and Tina Vilsb{\o}ll and Anders Junker and Stephan Sachs and Kerstin Stemmer and M{\"u}ller, {Timo D} and Tsch{\"o}p, {Matthias H} and Hofmann, {Susanna M} and Matthias Mann",

year = "2019",

month = mar,

doi = "10.15252/msb.20188793",

language = "English",

volume = "15",

journal = "Molecular Systems Biology",

issn = "1744-4292",

publisher = "Wiley-Blackwell",

}

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 - 2019/3

Y1 - 2019/3

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

SN - 1744-4292

VL - 15

JO - Molecular Systems Biology

JF - Molecular Systems Biology

M1 - e8793

ER -

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

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this