Analysis of Disease-Associated Protein Expression Using Quantitative Proteomics—Fibulin-5 Is Expressed in Association with Hepatic Fibrosis

Bracht, Thilo; Schweinsberg, Vincent; Trippler, Martin; Köhl, Michael; Ahrens, Maike; Padden, Juliet; Naboulsi, Wael; Barkovits, Katalin; Megger, Dominik A.; Eisenacher, Martin; Borchers, Christoph H.; Schlaak, J. F.; Hoffmann, Andreas-Claudius; Weber, Frank; Baba, Hideo A.; Meyer, Helmut E.; Sitek, Barbara

doi:10.1021/acs.jproteome.5b00053

Cited by 67 publications

(67 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, fibulin-5 was also shown to be increased in hepatic fibrosis. Both fibulin-5 protein and gene expression levels were associated with the severity of fibrosis, with the highest expression in liver biopsies with severe hepatic fibrosis compared to those with mild fibrosis, [7] suggesting that fibulin-5 is intrinsic to this fibrosis.…”

Section: Fibulin-5 and Its Relation With Diseasementioning

confidence: 99%

“…It would also be of interest to assess whether fibulin-5 (or its cleaved form) can be measured in sputum or serum in order to apply it as biomarker in COPD, similar to what was proposed for hepatic fibrosis. [7] An interesting example of a fibulin-5 target gene that may explain its role in fibrosis is transglutaminase 2 (TG2). TG2 is the most widely expressed TG and is involved in the crosslinking of ECM proteins such as elastin, collagen, and fibronectin.…”

Section: Expert Opinion: Fibulin-5 As a Therapeutic Targetmentioning

confidence: 99%

See 1 more Smart Citation

Fibulin-5 as a potential therapeutic target in COPD

Brandsma

Berge

Postma

et al. 2016

Expert Opinion on Therapeutic Targets

View full text Add to dashboard Cite

Section: Fibulin-5 and Its Relation With Diseasementioning

confidence: 99%

Section: Expert Opinion: Fibulin-5 As a Therapeutic Targetmentioning

confidence: 99%

Fibulin-5 as a potential therapeutic target in COPD

Brandsma

Berge

Postma

et al. 2016

Expert Opinion on Therapeutic Targets

View full text Add to dashboard Cite

“…It is abundant in HSCs and in fibrotic septa of human cirrhotic liver (Mölleken et al, 2009). The expression of MFAP4 in fibrotic liver increases with fibrosis stage both on gene transcript level and on protein level (Bracht et al, 2015). …”

Section: Proteins Associated With Elastic Fibersmentioning

confidence: 99%

Elastin in the Liver

Kanta

2016

Front. Physiol.

View full text Add to dashboard Cite

A characteristic feature of liver cirrhosis is the accumulation of large amounts of connective tissue with the prevailing content of type I collagen. Elastin is a minor connective tissue component in normal liver but it is actively synthesized by hepatic stellate cells and portal fibroblasts in diseased liver. The accumulation of elastic fibers in later stages of liver fibrosis may contribute to the decreasing reversibility of the disease with advancing time. Elastin is formed by polymerization of tropoelastin monomers. It is an amorphous protein highly resistant to the action of proteases that forms the core of elastic fibers. Microfibrils surrounding the core are composed of fibrillins that bind a number of proteins involved in fiber formation. They include microfibril-associated glycoproteins (MAGPs), microfibrillar-associated proteins (MFAPs) and fibulins. Lysyl oxidase (LOX) and lysyl oxidase-like proteins (LOXLs) are responsible for tropoelastin cross-linking and polymerization. TGF-β complexes attached to microfibrils release this cytokine and influence the behavior of the cells in the neighborhood. The role of TGF-β as the main profibrotic cytokine in the liver is well-known and the release of the cytokines of TGF-β superfamily from their storage in elastic fibers may affect the course of fibrosis. Elastic fibers are often studied in the tissues where they provide elasticity and resilience but their role is no longer viewed as purely mechanical. Tropoelastin, elastin polymer and elastin peptides resulting from partial elastin degradation influence fibroblastic and inflammatory cells as well as angiogenesis. A similar role may be performed by elastin in the liver. This article reviews the results of the research of liver elastic fibers on the background of the present knowledge of elastin biochemistry and physiology. The regulation of liver elastin synthesis and degradation may be important for the outcome of liver fibrosis.

show abstract

“…Lumican is a prerequisite for liver fibrosis [65] and the altered expression of lumican has 350 been associated with liver fibrosis [66] . Alpha-1-antiproteinase (A1AT) is the most 351 abundant liver-derived glycoprotein in plasma.…”

mentioning

confidence: 99%

Early urinary candidate biomarker discovery in a rat thioacetamide-induced liver fibrosis model

Zhang

Yuan

et al. 2017

Preprint

View full text Add to dashboard Cite

Biomarker is the change associated with the disease. Blood is relatively stable because of the homeostatic mechanisms of the body. However, urine accumulates changes of the body, which makes it a better early biomarker source. Liver fibrosis, which results from the deposition of extracellular matrix (ECM) components, is a reversible pathological condition, whereas cirrhosis, the end-stage of liver fibrosis, is irreversible. Consequently, noninvasive early biomarkers for fibrosis are desperately needed. In this study, differential urinary proteins were identified in the thioacetamide (TAA) liver fibrosis rat model using tandem mass tagging and two-dimensional liquid chromatography tandem mass spectrometry (2DLC-MS/MS). A total of 766 urinary proteins were identified, 143 and 118 of which were significantly changed in the TAA 1-week and 3-week groups, respectively. Multiple reaction monitoring (MRM)-targeted proteomics was used to further validate the abundant differentially expressed proteins in the TAA 1-week, 3-week, 6-week and 8-week groups. A total of 40 urinary proteins were statistically significant (fold change >2 and p<0.05), 15 of which had been previously reported as biomarkers of liver fibrosis, cirrhosis or other related diseases and 10 of which had been reported to be associated with the pathology and mechanism of liver fibrosis. These differential proteins were detected in urine before the alanine aminotransferase (ALT) and aspartate transaminase (AST) changes in the serum and before fibrosis was observed upon hematoxylin and eosin (HE) and Masson’s staining.

show abstract

Analysis of Disease-Associated Protein Expression Using Quantitative Proteomics—Fibulin-5 Is Expressed in Association with Hepatic Fibrosis

Cited by 67 publications

References 39 publications

Fibulin-5 as a potential therapeutic target in COPD

Fibulin-5 as a potential therapeutic target in COPD

Elastin in the Liver

Early urinary candidate biomarker discovery in a rat thioacetamide-induced liver fibrosis model

Contact Info

Product

Resources

About