An exploratory study examining how nano-liquid chromatography–mass spectrometry and phosphoproteomics can differentiate patients with advanced fibrosis and higher percentage collagen in non-alcoholic fatty liver disease
Zobair M. Younossi,Zobair M. Younossi,Azza Karrar,Azza Karrar,Mariaelena Pierobon,Aybike Birerdinc,Maria Stepanova,Maria Stepanova,Dinan Abdelatif,Dinan Abdelatif,Zahra Younoszai,Thomas Jeffers,Sean Felix,Kianoush Jeiran,Alex Hodge,Weidong Zhou,Fanny Monge,Fanny Monge,Lakshmi Alaparthi,Lakshmi Alaparthi,Vikas Chandhoke,Vikas Chandhoke,Zachary Goodman,Zachary Goodman,Emanuel F. Petricoin +24 more
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Simultaneous profiling of serum proteome and hepatic phosphoproteome reveals that the activation of ASK1 S38, p38 MAPK in the liver, and serum α2M and coagulation factor V are independently associated with hepatic collagen deposition in patients with NASH.Abstract:
Non-alcoholic steatohepatitis (NASH) is among the leading causes of liver disease worldwide. It is increasingly recognized that the phenotype of NASH may involve a number of different pathways, of which each could become important therapeutic targets. The aim of this study is to use high resolution mass spectrometry (MS) and phosphoproteomics techniques to assess the serum proteome and hepatic phosphoproteome in subjects with NASH-related fibrosis. Sixty-seven biopsy-proven NAFLD subjects with frozen sera and liver tissue were included. Reverse phase protein microarray was used to quantify the phosphorylation of key signaling proteins in liver and nano-liquid chromatography (LC)-MS was used to sequence target biomarkers in the serum. An image analysis algorithm was used to quantify the percentage of collagen (% collagen) using computer-assisted morphometry. Using multiple regression models, serum proteomes and phosphorylated hepatic proteins that were independently (p ≤ 0.05) associated with advanced fibrosis (stage ≥ 2) and higher % collagen were assessed. Phosphorylated signaling pathways in the liver revealed that apoptosis signal-regulating kinase 1, mitogen-activated protein kinase (ASK1-MAPK pathway involving ASK1 S38 (p < 0.02) and p38 MAPK (p = 0.0002)) activated by the inflammatory cytokine interleukin (IL-10) (p < 0.001), were independently associated with higher % collagen. LC-MS data revealed that serum alpha-2 macroglobulin (α2M) (p = 0.0004) and coagulation factor V (p = 0.0127) were independently associated with higher % hepatic collagen. Simultaneous profiling of serum proteome and hepatic phosphoproteome reveals that the activation of ASK1 S38, p38 MAPK in the liver, and serum α2M and coagulation factor V are independently associated with hepatic collagen deposition in patients with NASH. These data suggest the role of these pathways in the pathogenesis of NASH-related fibrosis as a potential therapeutic target.read more
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Journal ArticleDOI
The role of omics in the pathophysiology, diagnosis and treatment of non-alcoholic fatty liver disease.
TL;DR: The chief contributions of these techniques in understanding, diagnosing and treating NAFLD are summarized herein.
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Updates in the quantitative assessment of liver fibrosis for nonalcoholic fatty liver disease: Histological perspective.
Gwyneth Soon,Aileen Wee +1 more
TL;DR: SHG-microscopy shows promise as the new gold standard for the quantitative measurement of liver fibrosis, and the pivotal role of the liver biopsy is reaffirmed in fibrosis assessment in NAFLD, at least for the near-future.
Journal ArticleDOI
Mitogen Activated Protein Kinases in Steatotic and Non-Steatotic Livers Submitted to Ischemia-Reperfusion.
Mónica B. Jiménez-Castro,María Eugenia Cornide-Petronio,Jordi Gracia-Sancho,Araní Casillas-Ramírez,Carmen A. Peralta +4 more
TL;DR: Analysis of the participation of mitogen-activated protein kinases, namely p38, JNK and ERK 1/2 in steatotic and non-steatotic livers undergoing ischemia-reperfusion (I-R), suggests that further investigations are required to elucidate more extensively the mechanisms by which these kinases work in hepatic I-R.
Journal ArticleDOI
Diagnostic Modalities of Non-Alcoholic Fatty Liver Disease: From Biochemical Biomarkers to Multi-Omics Non-Invasive Approaches
TL;DR: This article provides a comprehensive review of the currently available and emerging non-invasive diagnostic tools used in assessing NAFLD, highlighting the importance of accurate and validated diagnostic tools.
Journal ArticleDOI
Protective function on liver and proteomic analysis of the improvement mechanism of Sedum sarmentosum Bunge extract on nonalcoholic fatty liver disease in Nile tilapia
TL;DR: This study reveals thatSSB extract has a hepatoprotective role in Nile tilapia with HFD-induced NAFLD, and the observed changes in the DEP profiles indicate that SSB exerts its protective effects via regulation of lipid metabolism, steroid biosynthesis, and apoptosis.
References
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Global epidemiology of nonalcoholic fatty liver disease—Meta‐analytic assessment of prevalence, incidence, and outcomes
Zobair M. Younossi,Zobair M. Younossi,Aaron B. Koenig,Dinan Abdelatif,Yousef Fazel,Linda Henry,Mark Wymer,Mark Wymer +7 more
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Naga Chalasani,Zobair M. Younossi,Joel E. Lavine,Anna Mae Diehl,Elizabeth M. Brunt,Kenneth Cusi,Michael Charlton,Arun J. Sanyal +7 more
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Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity.
Christi A. Matteoni,Zobair M. Younossi,Terry Gramlich,Navdeep Boparai,Yao Chang Liu,Arthur J. McCullough +5 more
TL;DR: The outcome of cirrhosis and liver-related death is not uniform across the spectrum of nonalcoholic fatty liver, and poor outcomes are more frequent in patients in whom biopsies show ballooning degeneration and Mallory hyaline or fibrosis.
Journal ArticleDOI
The NAFLD fibrosis score: A noninvasive system that identifies liver fibrosis in patients with NAFLD
Paul Angulo,Jason M. Hui,Giulio Marchesini,Ellisabetta Bugianesi,Jacob George,Geoffrey C. Farrell,Felicity Enders,Sushma Saksena,Alastair D. Burt,John P. Bida,Keith D. Lindor,Schuyler O. Sanderson,Marco Lenzi,Leon A. Adams,James G. Kench,Terry M. Therneau,Christopher P. Day +16 more
TL;DR: A simple scoring system accurately separates patients with nonalcoholic fatty liver disease with and without advanced fibrosis, rendering liver biopsy for identification ofAdvanced fibrosis unnecessary in a substantial proportion of patients.
Journal ArticleDOI
Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up.
Mattias Ekstedt,Hannes Hagström,Patrik Nasr,Mats Fredrikson,Per Stål,Stergios Kechagias,Rolf Hultcrantz +6 more
TL;DR: NAFLD patients have increased risk of death, with a high risk ofdeath from cardiovascular disease and liver‐related disease, and the NAS was not able to predict overall mortality, whereas fibrosis stage predicted both overall and disease‐specific mortality.
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