Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease.,Molecular Systems Biology

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Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease.
Molecular Systems Biology ( IF 8.5 ) Pub Date : 2019-03-01 , DOI: 10.15252/msb.20188793
Lili Niu _{1,

2} , Philipp E Geyer _{1,

2} , Nicolai J Wewer Albrechtsen _{1,

2,

3,

4,

5} , Lise L Gluud _{6,

7} , Alberto Santos ₁ , Sophia Doll _{1,

2} , Peter V Treit ₂ , Jens J Holst _{3,

4} , Filip K Knop _{4,

6,

8} , Tina Vilsbøll _{6,

8} , Anders Junker _{6,

8} , Stephan Sachs ₉ , Kerstin Stemmer ₉ , Timo D Müller ₉ , Matthias H Tschöp ₉ , Susanna M Hofmann _{10,

11,

12} , Matthias Mann _{2,

13}

Affiliation

Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Gastrounit, Medical Division, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.
Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup, Denmark.
Helmholtz Diabetes Center at Helmholtz Centre Munich & Division of Metabolic Diseases, Institute for Diabetes and Obesity, Technische Universität München, Munich, Germany.
Institute for Diabetes and Regeneration, Helmholtz Diabetes Center at Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
German Center for Diabetes Research (DZD), Neuherberg, Germany.
Medizinische Klinik und Poliklinik IV, Klinikum der LMU, München, Germany.
Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

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.

中文翻译：

血浆蛋白质组分析发现了与非酒精性脂肪肝相关的新型蛋白质。

非酒精性脂肪肝 (NAFLD) 影响着 25% 的人口，并且在治疗选择有限的情况下可能会发展为肝硬化。由于肝脏分泌大部分血浆蛋白，肝脏疾病可能会影响血浆蛋白质组。对 48 名患有或不患有肝硬化或 NAFLD 的患者进行的血浆蛋白质组分析显示，有 6 种统计上显着变化的蛋白质（ALDOB、APOM、LGALS3BP、PIGR、VTN 和 AFM），其中两种已经与肝脏疾病相关。聚合免疫球蛋白受体 (PIGR) 在 NAFLD 患者和肝硬化患者中均显着升高 170%，并在小鼠模型中得到进一步验证。此外，临床和蛋白质组数据的全球相关图谱将 DPP4、ANPEP、TGFBI、PIGR 和 APOE 与 NAFLD 和肝硬化密切相关。重要的糖尿病药物靶点 DPP4 是一种氨肽酶，如 ANPEP、ENPEP 和 LAP3，所有这些酶在人类或小鼠数据中均上调。此外，ANPEP 和 TGFBI 在纤维化的细胞外基质重塑中具有潜在作用。因此，血浆蛋白质组分析可以识别肝病中潜在的生物标志物和药物靶点。

更新日期：2020-02-18

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