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Condition: Liver Disease

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Total 328 results found since Jan 2013.

SIRT3 Regulates Hepatic Stellate Cell Activation Metabolism
In this study, we aimed to establish whether SIRT3 regulated the SDH activity, succinate, and GPR91 expression in HSCs and an animal model of NAFLD. Our goal was also to determine whether succinate released from hepatocytes regulated HSC activation. Inhibiting SIRT3 using SIRT3 siRNA exacerbated HSC activation via the SDH-succinate-GPR91 pathway, and SIRT3 overexpression or honokiol treatment attenuated HSC activation in vitro. In isolated liver and HSCs from methionine- and choline-deficient (MCD) diet-induced NAFLD, the expression of SIRT3 and SDH activity was decreased, and the succinate concentrations and GPR91 express...
Source: Journal of Biological Chemistry - May 5, 2016 Category: Chemistry Authors: Li, Y. H., Choi, D. H., Lee, E. H., Seo, S. R., Lee, S., Cho, E.-H. Tags: Cell Biology Source Type: research

Hedgehog signaling is a potent regulator of liver lipid metabolism and reveals a GLI-code associated with steatosis
This study assessed the unexpected role of the Hedgehog pathway in adult liver lipid metabolism. Using transgenic mice with conditional hepatocyte-specific deletion of Smoothened in adult mice, we showed that hepatocellular inhibition of Hedgehog signaling leads to steatosis by altering the abundance of the transcription factors GLI1 and GLI3. This steatotic 'Gli-code' caused the modulation of a complex network of lipogenic transcription factors and enzymes, including SREBP1 and PNPLA3, as demonstrated by microarray analysis and siRNA experiments and could be confirmed in other steatotic mouse models as well as in steatoti...
Source: eLife - May 17, 2016 Category: Biomedical Science Tags: Biochemistry Cell Biology Hedgehog signalling hepatocytes Human liver Mouse NAFLD smoothened steatotic Gli-code Source Type: research

Receptor interacting protein 3 protects mice from high fat diet‐induced liver injury
Conclusion: Absence of RIP3, a key mediator of necroptosis, exacerbated HFD‐induced liver injury, associated with increased inflammation and hepatocyte apoptosis, as well as early fibrotic responses. These findings indicate that shifts in the mode of hepatocellular death can influence disease progression and have therapeutic implications because manipulation of hepatocyte cell death pathways is being considered as a target for treatment of NAFLD. This article is protected by copyright. All rights reserved.
Source: Hepatology - June 14, 2016 Category: Internal Medicine Authors: Sanjoy Roychowdhury, Rebecca L. McCullough, Carlos Sanz‐Garcia, Paramananda Saikia, Naim Alkhouri, Ammar Matloob, Katherine Pollard, Megan R. McMullen, Colleen M. Croniger, Laura E. Nagy Tags: Steatohepatitis and Metabolic Liver Disease Source Type: research

Gene network activity in cultivated primary hepatocytes is highly similar to diseased mammalian liver tissue.
In conclusion, this study shows that gene regulatory network alterations of cultivated hepatocytes resemble those of inflammatory liver diseases and should therefore be considered and exploited as disease models. PMID: 27339419 [PubMed - as supplied by publisher]
Source: Archives of Toxicology - June 22, 2016 Category: Toxicology Authors: Godoy P, Widera A, Schmidt-Heck W, Campos G, Meyer C, Cadenas C, Reif R, Stöber R, Hammad S, Pütter L, Gianmoena K, Marchan R, Ghallab A, Edlund K, Nüssler A, Thasler WE, Damm G, Seehofer D, Weiss TS, Dirsch O, Dahmen U, Gebhardt R, Chaudhari U, Megana Tags: Arch Toxicol Source Type: research

Hepatocyte-protective effect of nectandrin B, a nutmeg lignan, against oxidative stress: Role of Nrf2 activation through ERK phosphorylation and AMPK-dependent inhibition of GSK-3 β.
This study investigated the hepatocyte-protective effect of nectandrin B against tert-butylhydroperoxide-induced oxidative injury and the underlying molecular mechanism. The cell viability assay revealed that nectandrin B prevents apoptosis stimulated by tert-butylhydroperoxide in both HepG2 cells and primary mouse hepatocytes. Nectandrin B also attenuated ROS production and restored the depleted glutathione level. Real-time PCR and immunoblot analyses showed that the expression of glutamate-cysteine ligase, an enzyme responsible for the glutathione biosynthesis, was induced by nectandrin B, indicating its indirect antioxi...
Source: Toxicology and Applied Pharmacology - August 6, 2016 Category: Toxicology Authors: Song JS, Kim EK, Choi YW, Oh WK, Kim YM Tags: Toxicol Appl Pharmacol Source Type: research

Rubicon inhibits autophagy and accelerates hepatocyte apoptosis and lipid accumulation in nonalcoholic fatty liver disease
Conclusion: Rubicon is overexpressed and plays a pathogenic role in NAFLD by accelerating hepatocellular lipoapoptosis and lipid accumulation, as well as inhibiting autophagy. Rubicon may be a novel therapeutic target for regulating NAFLD development and progression. This article is protected by copyright. All rights reserved.
Source: Hepatology - September 15, 2016 Category: Internal Medicine Authors: Satoshi Tanaka, Hayato Hikita, Tomohide Tatsumi, Ryotaro Sakamori, Yasutoshi Nozaki, Sadatsugu Sakane, Yuto Shiode, Tasuku Nakabori, Yoshinobu Saito, Naoki Hiramatsu, Keisuke Tabata, Tsuyoshi Kawabata, Maho Hamasaki, Hidetoshi Eguchi, Hiroaki Nagano, Tamo Tags: Steatohepatitis and Metabolic Liver Disease Source Type: research

HNF-4alpha Negatively Regulates Hepcidin Expression Through BMPR1A in HepG2 Cells.
In conclusion, the present study suggests that HNF-4α has a suppressive effect on hepcidin expression by inactivating the BMP pathway, specifically via BMPR1A, in HepG2 cells. PMID: 27660075 [PubMed - as supplied by publisher]
Source: Biological Trace Element Research - September 22, 2016 Category: Biology Authors: Shi W, Wang H, Zheng X, Jiang X, Xu Z, Shen H, Li M Tags: Biol Trace Elem Res Source Type: research

Dihydroartemisinin protects against alcoholic liver injury through alleviating hepatocyte steatosis in a farnesoid X receptor-dependent manner.
This study was aimed to explore the impact of DHA on ALD and further elaborate the underlying mechanisms. Gain- or loss-of-function analyses of FXR were applied in both in vivo and in vitro studies. Results demonstrated that DHA rescued FXR expression and activity in alcoholic rat livers. DHA also reduced serodiagnostic markers of liver injury, including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase. DHA improved alcohol-induced liver histological lesions, expression of inflammation genes, and inflammatory cell infiltration. In addition, DHA not only attenuated hyperl...
Source: Toxicology and Applied Pharmacology - December 5, 2016 Category: Toxicology Authors: Xu W, Lu C, Yao L, Zhang F, Shao J, Zheng S Tags: Toxicol Appl Pharmacol Source Type: research

Salvianolic acid B protects against chronic alcoholic liver injury via SIRT1-mediated inhibition of CRP and ChREBP in rats.
This study investigated the hepatoprotective effects of SalB in chronic alcoholic liver disease (ALD) and explored the related signaling mechanisms. In vivo, SalB treatment significantly attenuated ethanol-induced liver injury by blocking the elevation of serum aminotransferase activities and markedly decreased hepatic lipid accumulation by reducing serum and liver triglyceride (TG) and total cholesterol (TC) levels. Moreover, SalB treatment ameliorated ethanol-induced hepatic inflammation by decreasing the levels of hepatotoxic cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Importantly, SalB...
Source: Toxicology Letters - December 14, 2016 Category: Toxicology Authors: Zhang N, Hu Y, Ding C, Zeng W, Shan W, Fan H, Zhao Y, Shi X, Gao L, Xu T, Wang R, Gao D, Yao J Tags: Toxicol Lett Source Type: research

MiR-30c-5p ameliorates hepatic steatosis in leptin receptor-deficient (db/db) mice via down-regulating FASN.
In this study, we observed a significant reduction of miR-30c-5p in the liver of leptin receptor-deficient (db/db) mice. Remarkably, recombinant adeno-associated virus (rAAV)-mediated delivery of miR-30c-5p was sufficient to attenuate triglyceride accumulation and hepatic steatosis in db/db mice. Through computational prediction, KEGG analysis and Ago2 co-immunoprecipitation, we identified that miR-30c-5p directly targeted fatty acid synthase, a key enzyme in fatty acid biosynthesis. Moreover, down-regulation of FASN by siRNA attenuated some key features of NAFLD, including decreased triglyceride accumulate and lipid depos...
Source: Oncotarget - January 16, 2017 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Mutation of miR-21 targets endogenous lipoprotein receptor-related protein 6 and nonalcoholic fatty liver disease.
Authors: Li CP, Li HJ, Nie J, Chen X, Zhou X Abstract Nonalcoholic fatty liver disease (NAFLD) is a chronic disorder characterized by hepatic fat accumulation and abnormal lipid metabolism. Although miR-21 has been implicated in nonalcoholic fatty liver disease, it is unknown whether miR-21 could function as a therapeutic target. Here, we perform transfection analysis of miR-21 mimic or control mimic to evaluate the effects of miR-21 expression levels on human HepG2 nonalcoholic fatty liver cells. We used siRNA techniques to knock down miR-21 in HepG2 and control 293T cell lines, and then monitored lipid production...
Source: American Journal of Translational Research - March 27, 2017 Category: Research Tags: Am J Transl Res Source Type: research

P.05.4: Cancer Progression Control in Inflammatory Bowel Disease: Cyclin D1 and E2F1 Sirna Delivery by New Vectors
Source: Digestive and Liver Disease - March 15, 2017 Category: Gastroenterology Authors: I. Russo, S. Bochicchio, O. Piazza, A.A. Barba, G. Lamberti, A. Carrizzo, P. Zeppa, C. Vecchione, P. Iovino, C. Ciacci Tags: Posters Source Type: research

TWEAK/Fn14 promotes pro-inflammatory cytokine secretion in hepatic stellate cells via NF- κB/STAT3 pathways
In this study, we explored the role of TWEAK/Fn14 in activated human HSCs. The LX-2 cells were treated with TWEAK, and the expression of pro-inflammatory cytokines was assayed by enzyme-linked immunosorbent assay (ELISA) and real-time PCR (RT-PCR). Western blotting and RT-PCR were performed to evaluate the expression of Fn14 after TWEAK stimulation. Total and phosphorylated of inhibitor-κB (I-κB), nuclear factor kappa B (NF-κB), Janus kinase 2 (JAK2), and signal transducers and activators of transcription 3 (STAT3) were examined by western blotting after TWEAK stimulation and small interfering RNA (siRNA) transfection. ...
Source: Molecular Immunology - April 12, 2017 Category: Allergy & Immunology Source Type: research

A Novel Role of Astrocyte Elevated Gene ‐1 (AEG‐1) in Regulating Non‐alcoholic Steatohepatitis (NASH)
Conclusion: AEG‐1 might be a key molecule regulating initiation and progression of NASH. AEG‐1 inhibitory strategies might be developed as a potential therapeutic intervention in NASH patients. This article is protected by copyright. All rights reserved.
Source: Hepatology - April 24, 2017 Category: Internal Medicine Authors: Jyoti Srivastava, Chadia L. Robertson, Kareem Ebeid, Mikhail Dozmorov, Devaraja Rajasekaran, Rachel Mendoza, Ayesha Siddiq, Maaged A. Akiel, Nidhi Jariwala, Xue ‐Ning Shen, Jolene J. Windle, Mark A. Subler, Nitai D. Mukhopadhyay, Shah Giashuddin, Shobha Tags: Steatohepatitis and Metabolic Liver Disease Source Type: research

Orphan nuclear receptor Nur77 inhibits Poly (I:C)-triggered acute liver inflammation by inducing the ubiquitin-editing enzyme A20.
Authors: Li XM, Yang TY, He XS, Wang JR, Gan WJ, Zhang S, Li JM, Wu H Abstract Inflammation is a key contributor to various types of acute and chronic liver disease. We recently reported that lack of Nur77, an orphan nuclear receptor, contributes to the pathogenesis of inflammatory diseases including inflammatory bowel disease and sepsis. However, whether Nur77 plays a critical role in liver inflammation remains to be fully understood. Employing in vivo acute liver inflammation model in wild-type (Nur77+/+) and Nur77-/- mice, we here found that Nur77 deficiency dramatically increased the production of pro-inflammat...
Source: Oncotarget - May 26, 2017 Category: Cancer & Oncology Tags: Oncotarget Source Type: research