المؤلفون: Maria Teresa Koenen, Elisa Fabiana Brandt, Dawid Marcin Kaczor, Tim Caspers, Alexandra Catharina Anna Heinzmann, Petra Fischer, Daniel Heinrichs, Theresa Hildegard Wirtz, Christian Trautwein, Rory R Koenen, Marie-Luise Berres

المصدر: Biomolecules, Vol 12, Iss 5, p 698 (2022)

مصطلحات موضوعية: stellate cell, liver fibrosis, extracellular vesicles, non-alcoholic fatty liver disease, metabolic-associated fatty liver disease, Microbiology, QR1-502

الوصف: Hepatic steatosis and chronic hepatocyte damage ultimately lead to liver fibrosis. Key pathophysiological steps are the activation and transdifferentiation of hepatic stellate cells. We assessed the interplay between hepatocytes and hepatic stellate cells under normal and steatotic conditions. We hypothesized that hepatocyte-derived extracellular vesicles (EVs) modify the phenotype of stellate cells. By high speed centrifugation, EVs were isolated from conditioned media of the hepatocellular carcinoma cell line HepG2 under baseline conditions (C-EVs) or after induction of steatosis by linoleic and oleic acids for 24 h (FA-EVs). Migration of the human stellate cell line TWNT4 and of primary human stellate cells towards the respective EVs and sera of MAFLD patients were investigated using Boyden chambers. Phenotype alterations after incubation with EVs were determined by qRT-PCR, Western blotting and immunofluorescence staining. HepG2 cells released more EVs after treatment with fatty acids. Chemotactic migration of TWNT4 and primary hepatic stellate cells was increased, specifically towards FA-EVs. Prolonged incubation of TWNT4 cells with FA-EVs induced expression of proliferation markers and a myofibroblast-like phenotype. Though the expression of the collagen type 1 α1 gene did not change after FA-EV treatment, expression of the myofibroblast markers, e.g., α-smooth-muscle-cell actin and TIMP1, was significantly increased. We conclude that EVs from steatotic hepatocytes can influence the behavior, phenotypes and expression levels of remodeling markers of stellate cells and guides their directed migration. These findings imply EVs as operational, intercellular communicators in the pathophysiology of steatosis-associated liver fibrosis and might represent a novel diagnostic parameter and therapeutic target.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2218-273X/12/5/698Test; https://doaj.org/toc/2218-273XTest

الوصول الحر: https://doaj.org/article/4e8430abd24040baae0357b784214c65Test

المؤلفون: Theresa Hildegard Wirtz, Petra Fischer, Christina Backhaus, Irina Bergmann, Elisa Fabiana Brandt, Daniel Heinrichs, Maria Teresa Koenen, Kai Markus Schneider, Thomas Eggermann, Ingo Kurth, Christian Stoppe, Jürgen Bernhagen, Tony Bruns, Janett Fischer, Thomas Berg, Christian Trautwein, Marie-Luise Berres

المصدر: International Journal of Molecular Sciences, Vol 20, Iss 15, p 3753 (2019)

مصطلحات موضوعية: HCV, liver fibrosis, macrophage migration inhibitory factor, promoter polymorphisms, hepatocellular carcinoma, biomarker, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Two polymorphisms in the promoter region of macrophage migration inhibitory factor (MIF)—rs755622 and rs5844572—exhibit prognostic relevance in inflammatory diseases. The aim of this study was to investigate a correlation between these MIF promoter polymorphisms and the severity of hepatitis C virus (HCV)-induced liver fibrosis. Our analysis included two independent patient cohorts with HCV-induced liver fibrosis (504 and 443 patients, respectively). The genotype of the single nucleotide polymorphism (SNP) -173 G/C and the repeat number of the microsatellite polymorphism -794 CATT5−8 were determined in DNA samples and correlated with fibrosis severity. In the first cohort, homozygous carriers of the C allele in the rs755622 had lower fibrosis stages compared to heterozygous carriers or wild types (1.25 vs. 2.0 vs. 2.0; p = 0.03). Additionally, ≥7 microsatellite repeats were associated with lower fibrosis stages (p = 0.04). Comparable tendencies were observed in the second independent cohort, where fibrosis was assessed using transient elastography. However, once cirrhosis had been established, the C/C genotype and higher microsatellite repeats correlated with impaired liver function and a higher prevalence of hepatocellular carcinoma. Our study demonstrates that specific MIF polymorphisms are associated with disease severity and complications of HCV-induced fibrosis in a stage- and context-dependent manner.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/20/15/3753Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/0c1918c5c21a4b06bda870f754aa2169Test

المؤلفون: Maria Teresa Koenen, Jens Tischendorf

المصدر: Gastro-News. 9:32-38

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::87d905efd7466e5f11d34191f0d2317aTest
https://doi.org/10.1007/s15036-022-2514-2Test