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Soluble Endoglin as a Potential Biomarker of Nonalcoholic Steatohepatitis (NASH) Development, Participating in Aggravation of NASH-Related Changes in Mouse Liver
IC. Igreja Sá, K. Tripska, M. Hroch, R. Hyspler, A. Ticha, H. Lastuvkova, J. Schreiberova, E. Dolezelova, S. Eissazadeh, B. Vitverova, I. Najmanova, M. Vasinova, M. Pericacho, S. Micuda, P. Nachtigal
Language English Country Switzerland
Document type Journal Article
Grant support
17-31754A
Ministerstvo Zdravotnictví Ceské Republiky
CZ.02.1.01/0.0/0.0/16_019/0000841
Univerzita Karlova v Praze
1166119
Grantová Agentura, Univerzita Karlova
SVV 260 549
Univerzita Karlova v Praze
NV17-31754A
MZ0
CEP Register
Digital library NLK
Full text - Article
E-resources NLK Online Full text
Directory of Open Access Journals from 2000Free Medical Journals from 2000
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Links
PubMed
33261044
DOI
10.3390/ijms21239021
Knihovny.cz E-resources
- MeSH
- Alkaline Phosphatase metabolism MeSH
- Aspartate Aminotransferases metabolism MeSH
- Biomarkers blood metabolism MeSH
- Models, Biological MeSH
- Cholesterol blood metabolism MeSH
- Diet, High-Fat MeSH
- Endoglin blood metabolism MeSH
- Fructose MeSH
- Liver Cirrhosis blood complications pathology MeSH
- Liver metabolism pathology MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Mice MeSH
- Non-alcoholic Fatty Liver Disease blood complications metabolism MeSH
- Oxidative Stress MeSH
- Solubility MeSH
- Triglycerides metabolism MeSH
- Inflammation pathology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Nonalcoholic steatohepatitis (NASH) is characterized by hepatic steatosis with inflammation and fibrosis. Membrane endoglin (Eng) expression is shown to participate in fibrosis, and plasma concentrations of soluble endoglin (sEng) are increased in patients with hypercholesterolemia and type 2 diabetes mellitus. We hypothesize that NASH increases both hepatic Eng expression and sEng in blood and that high levels of sEng modulate cholesterol and bile acid (BA) metabolism and affect NASH progression. Three-month-old transgenic male mice overexpressing human sEng and their wild type littermates are fed for six months with either a high-saturated fat, high-fructose high-cholesterol (FFC) diet or a chow diet. Evaluation of NASH, Liquid chromatography-mass spectrometry (LC/MS) analysis of BA, hepatic expression of Eng, inflammation, fibrosis markers, enzymes and transporters involved in hepatic cholesterol and BA metabolism are assessed using Real-Time Quantitative Reverse Transcription Polymerase Chain reaction (qRT-PCR) and Western blot. The FFC diet significantly increases mouse sEng levels and increases hepatic expression of Eng. High levels of human sEng results in increased hepatic deposition of cholesterol due to reduced conversion into BA, as well as redirects the metabolism of triglycerides (TAG) to its accumulation in the liver, via reduced TAG elimination by β-oxidation combined with reduced hepatic efflux. We propose that sEng might be a biomarker of NASH development, and the presence of high levels of sEng might support NASH aggravation by impairing the essential defensive mechanism protecting NASH liver against excessive TAG and cholesterol accumulation, suggesting the importance of high sEng levels in patients prone to develop NASH.
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- $a Igreja Sá, Ivone Cristina $u Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, 500 05 Hradec Kralove, Czech Republic
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- $a Nonalcoholic steatohepatitis (NASH) is characterized by hepatic steatosis with inflammation and fibrosis. Membrane endoglin (Eng) expression is shown to participate in fibrosis, and plasma concentrations of soluble endoglin (sEng) are increased in patients with hypercholesterolemia and type 2 diabetes mellitus. We hypothesize that NASH increases both hepatic Eng expression and sEng in blood and that high levels of sEng modulate cholesterol and bile acid (BA) metabolism and affect NASH progression. Three-month-old transgenic male mice overexpressing human sEng and their wild type littermates are fed for six months with either a high-saturated fat, high-fructose high-cholesterol (FFC) diet or a chow diet. Evaluation of NASH, Liquid chromatography-mass spectrometry (LC/MS) analysis of BA, hepatic expression of Eng, inflammation, fibrosis markers, enzymes and transporters involved in hepatic cholesterol and BA metabolism are assessed using Real-Time Quantitative Reverse Transcription Polymerase Chain reaction (qRT-PCR) and Western blot. The FFC diet significantly increases mouse sEng levels and increases hepatic expression of Eng. High levels of human sEng results in increased hepatic deposition of cholesterol due to reduced conversion into BA, as well as redirects the metabolism of triglycerides (TAG) to its accumulation in the liver, via reduced TAG elimination by β-oxidation combined with reduced hepatic efflux. We propose that sEng might be a biomarker of NASH development, and the presence of high levels of sEng might support NASH aggravation by impairing the essential defensive mechanism protecting NASH liver against excessive TAG and cholesterol accumulation, suggesting the importance of high sEng levels in patients prone to develop NASH.
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- $a Nachtigal, Petr $u Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, 500 05 Hradec Kralove, Czech Republic
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