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84 Publications visible to you, out of a total of 84
A hierarchical regulatory network ensures stable albumin transcription under various pathophysiological conditions

Abstract

Not specified

Authors: Rilu Feng, Kejia Kan, Carsten Sticht, Yujia Li, Shanshan Wang, Hui Liu, Chen Shao, Stefan Munker, Hanno Niess, Sai Wang, Christoph Meyer, Roman Liebe, Matthias P. Ebert, Steven Dooley, Huiguo Ding, Honglei Weng

Date Published: 1st Dec 2022

Publication Type: Journal

Serum Glial Cell Line-Derived Neurotrophic Factor (sGDNF) Is a Novel Biomarker in Predicting Cirrhosis in Patients with Chronic Hepatitis B

Abstract (Expand)

Objectives. We assessed the potential of glial cell line-derived neurotrophic factor (GDNF) as a useful biomarker to predict cirrhosis in chronic hepatitis B (CHB) patients. Methods. A total of 735 …nts. Methods. A total of 735 patients from two medical centers (385 CHB patients and 350 healthy controls) were included to determine the association of serum and tissue GDNF levels with biopsy-proven cirrhosis. The diagnostic accuracy of serum GDNF (sGDNF) was estimated and compared with other indices of cirrhosis. Results. We showed significantly higher levels of sGDNF in CHB patients with fibrosis (28.4 pg/ml vs. 11.6 pg/ml in patients without) and patients with cirrhosis (33.8 pg/ml vs. 23.5 pg/ml in patients without). The areas under receiver operating curve (AUROCs) of sGDNF were 0.83 (95% confidence interval (CI): 0.80–0.87) for predicting liver fibrosis and 0.84 (95% CI: 0.79–0.89) for cirrhosis. Findings from the serum protein level and hepatic mRNA expression were consistent. Using the best cutoff to predict cirrhosis, we categorized the patients into sGDNF-high and sGDNF-low groups. The sGDNF-high group had significantly larger Masson’s trichrome and reticulin staining-positive area, higher Scheuer score, and METAVIR fibrosis stage (all p < 0.001 ) but not steatosis. On multivariable regression, sGDNF was independently associated with cirrhosis with an odds ratio of 6.98 (95% CI: 1.10–17.94). Finally, we demonstrated that sGDNF outperformed AST to platelet ratio index, FIB-4, fibroscore, forn index, and fibrometer in differentiating F4 vs. F3. Conclusion. Using serum, tissue mRNA, and biopsy data, our study revealed a significant potential of sGDNF as a novel noninvasive biomarker for cirrhosis in CHB patients.

Authors: Guangyue Yang, Liping Zhuang, Tiantian Sun, Yee Hui Yeo, Le Tao, Wei Zhang, Wenting Ma, Liu Wu, Zongguo Yang, Yanqin Yang, Dongying Xue, Jie Zhang, Rilu Feng, Ebert Matthias P., Steven Dooley, Ekihiro Seki, Ping Liu, Cheng Liu

Date Published: 9th Jul 2022

Publication Type: Journal

FOXA2 prevents hyperbilirubinaemia in acute liver failure by maintaining apical MRP2 expression

Abstract (Expand)

Objective Multidrug resistance protein 2 (MRP2) is a bottleneck in bilirubin excretion. Its loss is sufficient to induce hyperbilirubinaemia, a prevailing characteristic of acute liver failure (ALF) … characteristic of acute liver failure (ALF) that is closely associated with clinical outcome. This study scrutinises the transcriptional regulation of MRP2 under different pathophysiological conditions. Design Hepatic MRP2, farnesoid X receptor (FXR) and Forkhead box A2 (FOXA2) expression and clinicopathologic associations were examined by immunohistochemistry in 14 patients with cirrhosis and 22 patients with ALF. MRP2 regulatory mechanisms were investigated in primary hepatocytes, Fxr −/− mice and lipopolysaccharide (LPS)-treated mice. Results Physiologically, homeostatic MRP2 transcription is mediated by the nuclear receptor FXR/retinoid X receptor complex. Fxr −/− mice lack apical MRP2 expression and rapidly progress into hyperbilirubinaemia. In patients with ALF, hepatic FXR expression is undetectable, however, patients without infection maintain apical MRP2 expression and do not suffer from hyperbilirubinaemia. These patients express FOXA2 in hepatocytes. FOXA2 upregulates MRP2 transcription through binding to its promoter. Physiologically, nuclear FOXA2 translocation is inhibited by insulin. In ALF, high levels of glucagon and tumour necrosis factor α induce FOXA2 expression and nuclear translocation in hepatocytes. Impressively, ALF patients with sepsis express low levels of FOXA2, lose MRP2 expression and develop severe hyperbilirubinaemia. In this case, LPS inhibits FXR expression, induces FOXA2 nuclear exclusion and thus abrogates the compensatory MRP2 upregulation. In both Fxr −/− and LPS-treated mice, ectopic FOXA2 expression restored apical MRP2 expression and normalised serum bilirubin levels. Conclusion FOXA2 replaces FXR to maintain MRP2 expression in ALF without sepsis. Ectopic FOXA2 expression to maintain MRP2 represents a potential strategy to prevent hyperbilirubinaemia in septic ALF.

Authors: Sai Wang, Rilu Feng, Shan Shan Wang, Hui Liu, Chen Shao, Yujia Li, Frederik Link, Stefan Munker, Roman Liebe, Christoph Meyer, Elke Burgermeister, Matthias Ebert, Steven Dooley, Huiguo Ding, Honglei Weng

Date Published: 20th Apr 2022

Publication Type: Journal

Follistatin‐controlled activin‐HNF4α‐coagulation factor axis in liver progenitor cells determines outcome of acute liver failure

Abstract

Not specified

Authors: Tao Lin, Shanshan Wang, Stefan Munker, Kyounghwa Jung, Ricardo U. Macías‐Rodríguez, Astrid Ruiz‐Margáin, Robert Schierwagen, Hui Liu, Chen Shao, Chunlei Fan, Rilu Feng, Xiaodong Yuan, Sai Wang, Franziska Wandrer, Christoph Meyer, Ralf Wimmer, Roman Liebe, Jens Kroll, Long Zhang, Tobias Schiergens, Peter ten Dijke, Andreas Teufel, Alexander Marx, Peter R. Mertens, Hua Wang, Matthias P.A. Ebert, Heike Bantel, Enrico De Toni, Jonel Trebicka, Steven Dooley, Donghun Shin, Huiguo Ding, Hong‐Lei Weng

Date Published: 1st Feb 2022

Publication Type: Journal

Transforming growth factor β latency: A mechanism of cytokine storage and signalling regulation in liver homeostasis and disease

Abstract

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Authors: Yujia Li, Weiguo Fan, Frederik Link, Sai Wang, Steven Dooley

Date Published: 1st Feb 2022

Publication Type: Journal

Review series on Pathophysiology and Clinical Management of Alcoholic Liver Disease

Abstract

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Authors: Steven Dooley, Jonel Trebicka, Sebastian Mueller

Date Published: 18th Jan 2022

Publication Type: Journal

Inflammation in alcohol-associated liver disease progression

Abstract (Expand)

Abstract Chronic alcohol consumption induces stress and damage in alcohol metabolising hepatocytes, which leads to inflammatory and fibrogenic responses. Besides these direct effects, alcohol disrupts …ffects, alcohol disrupts intestinal barrier functions and induces gut microbial dysbiosis, causing translocation of bacteria or microbial products through the gut mucosa to the liver and, which induce inflammation indirectly. Inflammation is one of the key drivers of alcohol-associated liver disease progression from steatosis to severe alcoholic hepatitis. The current standard of care for the treatment of severe alcoholic hepatitis is prednisolone, aiming to reduce inflammation. Prednisolone, however improves only short-term but not long-term survival rates in those patients, and even increases the risk for bacterial infections. Thus, recent studies focus on the exploration of more specific inflammatory targets for the treatment of severe alcoholic hepatitis. These comprise, among others interference with inflammatory cytokines, modulation of macrophage phenotypes or targeting of immune cell communication, as summarized in the present overview. Although several approaches give promising results in preclinical studies, data robustness and ability to transfer experimental results to human disease is still not sufficient for effective clinical translation.

Authors: Sophie Lotersztajn, Antonio Riva, Sai Wang, Steven Dooley, Shilpa Chokshi, Bin Gao

Date Published: 18th Jan 2022

Publication Type: Journal

Liver specific, systemic and genetic contributors to alcohol-related liver disease progression

Abstract (Expand)

Abstract Alcohol-related liver disease (ALD) impacts millions of patients worldwide each year and the numbers are increasing. Disease stages range from steatosis via steatohepatitis and fibrosis to …epatitis and fibrosis to cirrhosis, severe alcohol-associated hepatitis and liver cancer. ALD is usually diagnosed at an advanced stage of progression with no effective therapies. A major research goal is to improve diagnosis, prognosis and also treatments for early ALD. This however needs prioritization of this disease for financial investment in basic and clinical research to more deeply investigate mechanisms and identify biomarkers and therapeutic targets for early detection and intervention. Topics of interest are communication of the liver with other organs of the body, especially the gut microbiome, the individual genetic constitution, systemic and liver innate inflammation, including bacterial infections, as well as fate and number of hepatic stellate cells and the composition of the extracellular matrix in the liver. Additionally, mechanical forces and damaging stresses towards the sophisticated vessel system of the liver, including the especially equipped sinusoidal endothelium and the biliary tract, work together to mediate hepatocytic import and export of nutritional and toxic substances, adapting to chronic liver disease by morphological and functional changes. All the aforementioned parameters contribute to the outcome of alcohol use disorder and the risk to develop advanced disease stages including cirrhosis, severe alcoholic hepatitis and liver cancer. In the present collection, we summarize current knowledge on these alcohol-related liver disease parameters, excluding the aspect of inflammation, which is presented in the accompanying review article by Lotersztajn and colleagues.

Authors: Bernd Schnabl, Gavin E. Arteel, Felix Stickel, Jan Hengstler, Nachiket Vartak, Ahmed Ghallab, Steven Dooley, Yujia Li, Robert F. Schwabe

Date Published: 18th Jan 2022

Publication Type: Journal

Cold shock protein YB-1 upregulates MDR1 transcription and thus contributes to cholangiocarcinoma chemoresistance to cisplatin

Abstract

Not specified

Authors: Tao Lin, Heng Liu, Jon Lindquist, Peter Mertens, Matthias Ebert, Steven Dooley, Jun Li, Stefan Munker, Honglei Weng

Date Published: 2022

Publication Type: Journal

Downregulation of ECM1 in hepatocytes as a damage response to liver injury

Abstract

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Authors: Yujia Li, Weronika Pioronska, Zeribe Nwosu, Weiguo Fan, MatthiasP.A. Ebert, Steven Dooley, Sai Wang

Date Published: 2022

Publication Type: Journal

FOXA2 inhibits hyperbilirubinemia through maintaining apical MRP2 expression in acute liver failure

Abstract

Not specified

Authors: Sai Wang, Rilu Feng, Shanshan Wang, Hui Liu, Chen Shao, Yujia Li, Link Frederik, Stefan Munker, Roman Liebe, Christoph Meyer, Elke Burgermeister, Matthias Ebert, Steven Dooley, Huiguo Ding, Honglei Weng

Date Published: 2022

Publication Type: Journal

Circulating miR-148a is a precipitant independent biomarker of acute-on-chronic liver failure (ACLF)

Abstract

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Authors: Maximilian Tessenyi, SusanneN Weber, Matthias Reichert, SenemC. Karatayli, RabeaA Hall, Tony Bruns, Sen Qiao, Ulrich Boehm, Steven Dooley, Frank Lammert, Ersin Karatayli

Date Published: 2022

Publication Type: Journal

Insulin-controlled C/EBPα expression determines the impact of TGF-β on HNF4α transcription in hepatocytes

Abstract

Not specified

Authors: Rilu Feng, Carsten Sticht, Kejia Kan, Stefan Munker, MatthiasP. Ebert, Steven Dooley, Hong-Lei Weng

Date Published: 2022

Publication Type: Journal

Multi-omics profiling identifies molecular signatures of acute-on-chronic liver failure in Abcb4KO mice upon chemical intoxication

Abstract

Not specified

Authors: Pia Erdoesi, Maren Buettner, Matthias Meyer-Bender, Rizqah Kamies, IoannisK. Deligiannis, MichaelP. Menden, Steven Dooley, CeliaP. Martinez-Jimenez, Christoph Ogris, Seddik Hammad

Date Published: 2022

Publication Type: Journal

Liver sinusoidal endothelial cells suppress BMP2 production in response to TGFβ pathway activation

Abstract

Not specified

Authors: Silvia Colucci, Sandro Altamura, Oriana Marques, Anne Dropmann, Natalie K. Horvat, Katja Müdder, Seddik Hammad, Steven Dooley, Martina U. Muckenthaler

Date Published: 13th May 2021

Publication Type: Journal

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