Detection of Novel Biomarkers of Liver Cirrhosis by Proteomic Analysis

Mölleken, Christian; Sitek, Barbara; Henkel, Corinna; Poschmann, Gereon; Sipos, Béla; Wiese, Signe; Warscheid, B.; Reiser, Markus; Friedman, Scott L.; Tornøe, Ida; Schlosser, A.; Klöppel, G.; Schmiegel, Wolff-Helmut; Meyer, H. E.; Holmskov, Uffe

doi:10.1055/s-0029-1191789

Cited by 30 publications

(43 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transgelin expression has been shown to be upregulated in fibrotic areas of hepatic sections from patients with liver cirrhosis showing intense staining in broad cirrhotic septa. In contrast, in normal liver, transgelin is expressed in the wall of blood vessels, in portal areas, and in some fibroblasts in portal areas but not in epithelial cells and hepatocytes (23). Transgelin expression was also found to be upregulated in the lungs of patients with idiopathic pulmonary fibrosis, and its expression was localized to fibroblastic foci and smooth muscle (34).…”

Section: Discussionmentioning

confidence: 89%

Extracellular matrix composition significantly influences pancreatic stellate cell gene expression pattern: role of transgelin in PSC function

Apte

Yang

Phillips

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Activated pancreatic stellate cells (PSCs) are responsible for the fibrotic matrix of chronic pancreatitis and pancreatic cancer. In vitro protocols examining PSC biology have usually involved PSCs cultured on plastic, a nonphysiological surface. However, PSCs cultured on physiological matrices, e.g., Matrigel (normal basement membrane) and collagen (fibrotic pancreas), may have distinctly different behaviors compared with cells cultured on plastic. Therefore, we aimed to 1) compare PSC gene expression after culture on plastic, Matrigel, and collagen I; 2) validate the gene array data for transgelin, the most highly dysregulated gene in PSCs grown on activating vs. nonactivating matrices, at mRNA and protein levels; 3) examine the role of transgelin in PSC function; and 4) assess transgelin expression in human chronic pancreatitis sections. Culture of PSCs on different matrices significantly affected their gene expression pattern. 146, 619, and 432 genes, respectively, were differentially expressed (P < 0.001) in PSCs cultured on collagen I vs. Matrigel, Matrigel vs. plastic, and collagen I vs. plastic. The highest fold change (12.5-fold upregulation) in gene expression in cells on collagen I vs. Matrigel was observed for transgelin (an actin stress fiber-associated protein). Transgelin was significantly increased in activated PSCs vs. quiescent PSCs. Silencing transgelin expression decreased PSC proliferation and also reduced platelet-derived growth factor-induced PSC migration. Notably, transgelin was highly expressed in chronic pancreatitis in stromal areas and periacinar spaces but was absent in acinar cells. These findings suggest that transgelin is a potentially useful target protein to modulate PSC function so as to ameliorate pancreatic fibrosis.

show abstract

Section: Discussionmentioning

confidence: 89%

Extracellular matrix composition significantly influences pancreatic stellate cell gene expression pattern: role of transgelin in PSC function

Apte

Yang

Phillips

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…Serum tests [12][13][14][15] and various imaging methods such as ultrasound elastography or magnetic resonance (MR) spectroscopy, MR diffusion and MR elastography [16] have been investigated for staging and diagnosing liver disease. However, MR relaxometry appears to be a promising tool for analysing disease processes in other organ systems [17], and there is evidence that indicates its usefulness in detecting liver disease [18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

MR relaxometry of the liver: significant elevation of T1 relaxation time in patients with liver cirrhosis

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Recent studies evaluating two-dimensional gel electrophoresis coupled to mass spectrometry to differentiate fibrosis stages in CHC infection have identified new proteins of interest such as Mac-3-binding protein, hemopexin, fetuin-A, and Noninvasive tools to assess liver disease Patel 229 leucine-rich a-2 glycoprotein [29 ]. A tissue-based proteomics study [30] using microdissection of cirrhotic septa revealed microfibril-associated protein 4 as a candidate biomarker that predicts cirrhosis in CHC patients with a high degree of accuracy. Validation of these candidate proteins, along with issues regarding cost, reproducibility, and high-throughput capability, will need to be addressed in future studies.…”

Section: Genetic Markers Of Disease Progression and Proteomicsmentioning

confidence: 99%